alzheimer's disease research

Alzheimer's Disease Research Center

Guidelines for reducing dementia risk

Mayo Clinic contributed to the recently released World Health Organization publication that provides evidence-based guidance for a public health response to dementia. Read the report (PDF).

A letter from the director

Center director Ronald C. Petersen, M.D., Ph.D., provides an update on brain health and research. Read the update in the center's newsletter (PDF).

Mayo Clinic Conference on Brain Health and Dementia

The Nov. 4, 2023, Mayo Clinic Conference on Brain Health and Dementia explored paths to emotional wellness for participants and those living with dementia. Read more.

Peer-to-peer support for dementia caregivers

Mayo Clinic researchers are studying the effectiveness of peer-to-peer caregiver matching for mutual emotional support. Find enrollment information for interested participants or study information for researchers .

Coordinating Center: Lewy body dementia

The Alzheimer's Disease Research Center at Mayo Clinic in Rochester, Minnesota, is the Coordinating Center for the Lewy Body Dementia Association Research Centers of Excellence network.

The Alzheimer's Disease Research Center at Mayo Clinic promotes research and education about healthy brain aging, mild cognitive impairment, Alzheimer's disease, Lewy body dementia, frontotemporal dementia and other related dementia disorders.

The Alzheimer's Disease Research Center, which is jointly based at the Mayo Clinic campuses in Jacksonville, Florida, and Rochester, Minnesota, also provides care and services for patients with dementia disorders and their families.

Ultimately, researchers in the Alzheimer's Disease Research Center hope to prevent, delay and possibly cure Alzheimer's disease and other dementia disorders.

In creative, interdisciplinary collaboration, researchers in the Alzheimer's Disease Research Center conduct a wide range of investigations, such as the molecular workings of memory and clinical trials that test new drugs. The center is a leader in classifying and diagnosing different forms of early-stage cognitive changes and identifying predictive models of risk. The center also trains new scientists.

The Alzheimer's Disease Research Center also studies the entire spectrum of aging, including typical aging, mild cognitive impairment and dementia, in cooperation with the Mayo Clinic Study of Aging .

Research in the Alzheimer's Disease Research Center has led to the detection of biomarkers and advanced neuroimaging tests, in turn paving the way for potential new prevention therapies and treatments for early Alzheimer's disease.

Research Center of Excellence

The Alzheimer's Disease Research Center at Mayo Clinic's campus in Rochester, Minnesota, is a Lewy Body Dementia Association Research Center of Excellence and serves as the Coordinating Center for the entire Lewy Body Dementia Association Research Centers of Excellence program. This program currently consists of 33 of the nation's leading Lewy body dementia research institutions, which are committed to providing advanced Lewy body dementia care, community outreach and support.

Learn more about the Lewy Body Dementia Association Research Centers of Excellence .

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Patient support

For patients and families affected by Alzheimer's disease or a related dementia, the Alzheimer's Disease Research Center at Mayo Clinic offers:

• Opportunities to participate in drug trials, clinical research projects, special programs, support groups and education events
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The director of the Alzheimer's Disease Research Center is Ronald C. Petersen, M.D., Ph.D.

The Mayo Clinic Alzheimer's Disease Research Center is one of 29 Alzheimer's disease centers in the U.S. funded by the National Institute on Aging.

Although each of the Alzheimer's disease centers has a unique focus, a common goal is to enhance research by sharing ideas, innovative strategies and research results.

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Innovative strategies drive neuroscience research across the spectrum of aging, from healthy aging to dementia.

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The center offers a variety of conferences, programs and events as well as a website, Dementia Hub, for research participants, patients, families and the community.

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Alzheimer's Research & Therapy

Announcing the launch of mini reviews.

Concise overview articles of key topics in neurodegeneration, which can be read wherever you are, whenever suits you. 

Find out more here . 

New Thematic Series - AI in Dementia

Alzheimer's Research & Therapy presents a thematic series focusing on the use of artificial intelligence, machine learning and related techniques in dementia research. 

Find out more about the series  here .

• Most accessed

Alzheimer’s and neurodegenerative disease biomarkers in blood predict brain atrophy and cognitive decline

Authors: Heather E. Dark, Yang An, Michael R. Duggan, Cassandra Joynes, Christos Davatzikos, Guray Erus, Alexandria Lewis, Abhay R. Moghekar, Susan M. Resnick and Keenan A. Walker

Utilization of fluid-based biomarkers as endpoints in disease-modifying clinical trials for Alzheimer’s disease: a systematic review

Authors: Marlies Oosthoek, Lisa Vermunt, Arno de Wilde, Bram Bongers, Daniel Antwi-Berko, Philip Scheltens, Pieter van Bokhoven, Everard G. B. Vijverberg and Charlotte E. Teunissen

Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea

Authors: Min Young Chun, Wonjeong Chae, Sang Won Seo, Hyemin Jang, Jihwan Yun, Duk L. Na, Dongwoo Kang, Jungkuk Lee, Dustin B. Hammers, Liana G. Apostolova, Sung-In Jang and Hee Jin Kim

Association of midlife body-weight variability and cycles with earlier dementia onset: a nationwide cohort study

Authors: Yujin Park, Su Hwan Kim, Jiwon Ryu and Hyung-Jin Yoon

Associations of plasma neurofilament light chain with cognition and neuroimaging measures in community-dwelling early old age men

Authors: Rongxiang Tang, Erik Buchholz, Anders M. Dale, Robert A. Rissman, Christine Fennema-Notestine, Nathan A. Gillespie, Donald J Hagler Jr, Michael J. Lyons, Michael C. Neale, Matthew S. Panizzon, Olivia K. Puckett, Chandra A. Reynolds, Carol E. Franz, William S. Kremen and Jeremy A. Elman

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Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APP/PS1 transgenic mice

Authors: Bin Li, Maria E Gonzalez-Toledo, Chun-Shu Piao, Allen Gu, Roger E Kelley and Li-Ru Zhao

Cerebral microbleeds: overview and implications in cognitive impairment

Authors: Sergi Martinez-Ramirez, Steven M Greenberg and Anand Viswanathan

BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease

Authors: Robert Vassar

A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody

Authors: Chad J. Swanson, Yong Zhang, Shobha Dhadda, Jinping Wang, June Kaplow, Robert Y. K. Lai, Lars Lannfelt, Heather Bradley, Martin Rabe, Akihiko Koyama, Larisa Reyderman, Donald A. Berry, Scott Berry, Robert Gordon, Lynn D. Kramer and Jeffrey L. Cummings

The Correction to this article has been published in Alzheimer's Research & Therapy 2022 14 :70

Alzheimer’s disease drug-development pipeline: few candidates, frequent failures

Authors: Jeffrey L Cummings, Travis Morstorf and Kate Zhong

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Early Career Researcher Reviewer Panel

Interested in an introduction to peer reviewing articles for Alzheimer's Research & Therapy?

Find out more about our ECR Peer Reviewer Panel!

Aims and scope

Alzheimer's Research & Therapy is the major forum for translational research into Alzheimer's disease. An international peer-reviewed journal, it publishes open access basic research with a translational focus, as well as clinical trials, research into drug discovery and development, and epidemiologic studies. The journal also provides reviews, viewpoints, commentaries, debates and reports.

Although the primary focus is Alzheimer's disease, the scope encompasses translational research into other neurodegenerative diseases.

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10 Years of Alzheimer's Research & Therapy

Subject Cognitive Decline

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2022 Citation Impact 9.0 - 2-year Impact Factor 9.2 - 5-year Impact Factor 1.849 - SNIP (Source Normalized Impact per Paper) 2.650 - SJR (SCImago Journal Rank)

2023 Speed 15 days submission to first editorial decision for all manuscripts (Median) 152 days submission to accept (Median)

2023 Usage  1,914,774 downloads 2,982 Altmetric mentions

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ISSN: 1758-9193

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Study Suggests Treatments that Unleash Immune Cells in the Brain Could Help Combat Alzheimer’s

Posted on April 25th, 2024 by Dr. Monica M. Bertagnolli

In Alzheimer’s disease, a buildup of sticky amyloid proteins in the brain clump together to form plaques, causing damage that gradually leads to worsening dementia symptoms. A promising way to change the course of this disease is with treatments that clear away damaging amyloid plaques or stop them from forming in the first place. In fact, the Food and Drug Administration recently approved the first drug for early Alzheimer’s that moderately slows cognitive decline by reducing amyloid plaques. 1 Still, more progress is needed to combat this devastating disease that as many as 6.7 million Americans were living with in 2023.

Recent findings from a study in mice, supported in part by NIH and reported in Science Translational Medicine , offer another potential way to clear amyloid plaques in the brain. The key component of this strategy is using the brain’s built-in cleanup crew for amyloid plaques and other waste products: immune cells known as microglia that naturally help to limit the progression of Alzheimer’s. The findings suggest it may be possible to develop immunotherapies—treatments that use the body’s immune system to fight disease—to activate microglia in the brains of people with Alzheimer’s and clear amyloid plaques more effectively. 2

In their report, the research team—including Marco Colonna , Washington University School of Medicine in St. Louis, and Jinchao Hou, now at Children’s Hospital of Zhejiang University School of Medicine in Zhejiang Province, China—wrote that microglia in the brain surround plaques to create a barrier that controls their spread. Microglia can also destroy amyloid plaques directly. But how microglia work in the brain depends on a fine-tuned balance of signals that activate or inhibit them. In people with Alzheimer’s, microglia don’t do their job well enough.  

The researchers suspected this might have something to do with a protein called apolipoprotein E (APOE). This protein normally helps carry cholesterol and other fats in the bloodstream. But the gene encoding the protein is known for its role in influencing a person’s risk for developing Alzheimer’s, and in the Alzheimer’s brain, the protein is a key component of amyloid plaques. The protein can also inactivate microglia by binding to a receptor called LILRB4 found on the immune cells’ surfaces.

Earlier studies in mouse models of Alzheimer’s showed that the LILRB4 receptor is expressed at high levels in microglia when amyloid plaques build up. This suggested that treatments targeting this receptor on microglia might hold promise for treating Alzheimer’s. In the new study, the research team looked for evidence that an increase in LILRB4 receptors on microglia plays an important role in the brains of people with Alzheimer’s.

To do this, the researchers first studied brain tissue samples from people who died with this disease and discovered unusually high amounts of the LILRB4 receptor on the surfaces of microglia, similar to what had been seen in the mouse models. This could help explain why microglia struggle to control amyloid plaques in the Alzheimer’s brain.

Next, the researchers conducted studies of mouse brains with accumulating amyloid plaques that express the LILRB4 receptor to see if an antibody targeting the receptor could lower amyloid levels by boosting activity of immune microglia. Their findings suggest that the antibody treatment blocked the interaction between APOE proteins and LILRB4 receptors and enabled microglia to clear amyloid plaques. Intriguingly, the team’s additional studies found that this clearing process also changed the animals’ behavior, making them less likely to take risks. That’s important because people with Alzheimer’s may engage in risky behaviors as they lack memories of earlier experiences that they could use to make decisions.

There’s plenty more to learn. For instance, the researchers don’t know yet whether this approach will affect the tau protein , which forms damaging tangles inside neurons in the Alzheimer’s brain. They also want to investigate whether this strategy of clearing amyloid plaques might come with other health risks.

But overall, these findings add to evidence that immunotherapies of this kind could be a promising way to treat Alzheimer’s. This strategy may also have implications for treating other neurodegenerative conditions characterized by toxic debris in the brain, such as Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Huntington’s disease. The hope is that this kind of research will ultimately lead to more effective treatments for Alzheimer’s and other conditions affecting the brain.

References:

[1] FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval . U.S. Food and Drug Administration (2023).

[2] Hou J, et al . Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model . Science Translational Medicine . DOI: 10.1126/scitranslmed.adj9052 (2024).

NIH Support: National Institute of General Medical Sciences, National Institute on Aging

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Posted In: Health , News , Science

Tags: Alzheimer's treatment , Alzheimer’s disease , amyloid , basic research , brain , microglia , neurons , neuroscience

so, whats next? is it available? how to obtain this??

Keep up the good work

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Alzheimer's disease research.

Driving innovative research around the world to end Alzheimer’s , we identify high-risk, high-reward projects that have the most promise to change the trajectory of the disease.

Our 360° Approach to Research

Tangling with tau, battling amyloid beta, blood and the brain in dementia, immunity and inflammation, biology of apoe and lipids, new approaches.

BrightFocus takes a 360 ° approach to fund innovative scientific research worldwide to defeat Alzheimer’s, exploring the full range of scientific paths toward better treatments and ultimately a cure. Watch this video and learn more.

Genes are the “master blueprint” that instructs our cells to make unique proteins which in turn build, operate, and repair human tissue. Humans have an estimated 24,000 genes along our 23 matched pairs of chromosomes (46 in all), and “genomics” refers to the field that studies all of them at once.

A biological marker (biomarker) is a measurable substance in an organism whose presence is indicative of some phenomenon such as disease or infection. Biomarkers can help doctors and scientists diagnose diseases and health conditions, find health risks in a person, monitor responses to treatment, and see how a person's disease or health condition changes over time.

Tau is a small protein with a short name but a large reputation because of its association with multiple brain diseases, including Alzheimer’s disease (AD). The tau protein is predominantly found in brain cells (neurons).

There are many versions of amyloid protein in the human body, and most serve a useful role. One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of amyloid plaques (abnormally configured proteins) between nerve cells (neurons) in the brain.

Scientists are interested in developing a screening tool for Alzheimer’s disease (AD) in blood. A simple blood draw is much less invasive than a spinal tap and may prove more cost effective. Developing blood biomarkers that accurately depict brain changes has proven challenging, as levels of AD hallmark proteins in the blood are low, but there are some very recent promising results observing tau and the ratio of Aβ42 and Aβ40.

One theory about Alzheimer’s disease (AD) is that it may be triggered, in part, by a breakdown in the brain’s immune system.

Alzheimer's disease (AD). Its primary function is to regulate a class of proteins involved in the metabolism of fats (lipids) in the body. However, APOE has several common variants (or "alleles") whose effect vary.

The human brain has an estimated 100 billion neurons. Extending from each of them is a long fiber, known as an “axon,” which can run several feet. Each axon forms a connection, known as a “synapse” with another neuron, creating a circuit over which brain signals travel. In Alzheimer’s disease (AD), individual neurons die and do not regenerate; while others have brains that are more are resilient and respond to meeting changing demands.

Years of innovative and dedicated research have paid off with the discovery of numerous factors contributing to Alzheimer’s disease (AD) pathology. With a disease as complex as this one, it’s very helpful to find multiple points where it may be possible to slow or halt its progress.

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Well-designed research pays off. With further research, each of these discoveries may contribute to the development of new treatments and preventions.

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Alzheimer's disease is the seventh leading cause of death in the United States. An irreversible degeneration of the brain that causes disruptions in memory, cognition, personality, and other functions, it eventually leads to death from complete brain failure.

Nearly 7 million Americans aged 65 and older are thought to have Alzheimer's disease. By 2050, that figure may increase to nearly 13 million.

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It is often said that “the eyes are the window to the soul,” and while that may or may not be true, the eye is certainly a window into many health conditions.

In fact, sometimes an eye doctor will be the first physician to diagnose a medical condition because the first signs may appear in the eye. Thus, having your eyes thoroughly examined is a lot more than just getting a prescription for new glasses or contact lenses.

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Basic science research featured at 2024 Vanderbilt Alzheimer’s Disease Research Day

Alexandra Scammell

Apr 24, 2024, 12:50 PM

On April 10, 2024, the Vanderbilt Memory and Alzheimer’s Center hosted its fifth Annual Vanderbilt Alzheimer’s Disease Research Day, which included faculty presentations, data blitzes, a keynote presentation, and a poster reception with more than 45 posters. “Big data” was the theme of this year’s VMAC event, but any research touching on Alzheimer’s disease and dementia was welcome.

Several School of Medicine Basic Sciences faculty presented at Alzheimer’s Disease Research Day this year, including Angela Kruse , research instructor in the Department of Cell and Developmental Biology, and Timothy J. Hohman , professor of pharmacology.

In her presentation titled “Multimodal Imaging Mass Spectrometry: Connecting Omics and Imaging to Discover Molecular Drivers of Health and Disease,” Kruse highlighted the work of Claire Scott , graduate student in the Department of Cell and Developmental Biology. “Claire [said] she would heckle me if I made a mistake presenting her data,” Kruse admitted good-naturedly.

Scott’s research focuses on white matter hyperintensities, which indicate lesions in the white matter of the brain and are visible on MRI scans. “They are associated with lower cognition in Alzheimer’s disease and, importantly, they start to show up in individuals far before the development of cognitive symptoms,” Kruse said. But beyond associations with cognitive decline in Alzheimer’s disease patients, the molecular environments of white matter hyperintensities and the background of their formation is poorly understood.

“My research aims to address this knowledge gap by applying a multimodal approach to human Alzheimer’s disease brain tissue,” Scott explained after Kruse’s presentation. She combines MRI, imaging mass spectrometry, immunofluorescent microscopy, among other methods to perform her research. As more data are collected, Scott can begin to computationally distinguish the lipid alterations most indicative of white matter hyperintensities across human donors and investigate the metabolic pathways involved in these changes.

“I thoroughly enjoyed discussing my work with such thoughtful people,” Scott said about the event’s attendees. “The conversations were invigorating and I’m excited to pursue avenues that [we] discussed.”

Presentations continued throughout the day. Hohman, in his talk, discussed the ways experts analyze and integrate data from demographics, imaging, genetics, fluid biomarkers, and the clinic to create various disease models. The “hope and goal is to use these different layers of information” to provide personalized treatment for Alzheimer’s disease.

“We are pretty multidisciplinary team,” Hohman said. “We have folks on the team who focus entirely on genomics. We have people on the team who focus primarily on neuroimaging and cognitive phenotypes. Then we have folks who focus on multi-omics—transcriptomics and proteomics—and integration of the two of these.”

The all-day event also included poster and “data blitz” presentations. Various Basic Sciences community members participated, including Neil Dani , assistant professor of cell and developmental biology, Jared Phillips , graduate student in pharmacology, and Yuting Tan , postdoc in the molecular physiology and biophysics.

For Scott, Alzheimer’s Disease Research Day allowed her to make connections that will help her incorporate more human brain tissue samples into her research. Plus, she learned more about how and what patient data is collected in certain cohorts. For Scott, learning about current data management principles was “very interesting” and, as a researcher, was glad for the opportunity to learn about it. “Overall, I was struck by how nicely the research presented in talks and posters seemed to dovetail in powerful ways,” she said.

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Alzheimer's disease was first described in 1906. Since then, scientists have made remarkable strides in understanding how Alzheimer's affects the brain and learning how to make life better for affected individuals and families. Below are some important milestones in our progress, including the founding of the Alzheimer's Association in 1980, which has played a key role in advancing research and raising awareness of the disease. 

1906-1960: First discovery

1970-1979: modern research, 1980-1989: awareness and momentum, 1990-1999: treatments emerge, 2000-2009: progress and hope, 2010-2019: setting a national agenda, 2020-present: a new era of treatment, dr. alois alzheimer first describes "a peculiar disease".

German physician Alois Alzheimer, a pioneer in linking symptoms to microscopic brain changes, describes the haunting case of Auguste D., a patient who had profound memory loss, unfounded suspicions about her family, and other worsening psychological changes. In her brain at autopsy, he saw dramatic shrinkage and abnormal deposits in and around nerve cells. Dr. Alzheimer died in 1915, never suspecting that his encounter with Auguste D. would one day touch the lives of millions and ignite a massive international research effort. Scientists recognize Dr. Alzheimer not only for his groundbreaking characterization of a major disease but also as a role model. He set a new standard for understanding neurodegenerative disorders by establishing a close clinical relationship with his patients and using new scientific tools to determine how symptoms related to physical brain changes.

Alzheimer's disease named

Emil Kraepelin, a German psychiatrist who worked with Dr. Alzheimer, first names "Alzheimer's Disease" in the eighth edition of his book "Psychiatrie."

Invention of electron microscope allows further study of brain

In 1931, Germans Max Knoll and Ernst Ruska co-invent the electron microscope, which can magnify up to 1 million times. It is not until after WWII that the electron microscope becomes common in major research settings, enabling scientists to study brain cells in more detail.

Development of cognitive measurement scales

Researchers develop the first validated measurement scale for assessing cognitive and functional decline in older adults, paving the way to correlate the level of measured impairment with estimates of the number of brain lesions and the volume of damaged tissue.

Founding of National Institute on Aging

An act of Congress establishes the National Institute on Aging (NIA) as one of our National Institutes of Health (NIH). The NIA is our primary federal agency supporting Alzheimer's research.

Alzheimer's recognized as most common cause of dementia

Neurologist Robert Katzman identifies Alzheimer's disease as the most common cause of dementia and a major public health challenge in his editorial published in Archives of Neurology.

Alzheimer's Association founded

In 1979, Jerome H. Stone and representatives from several family support groups met with the National Institute on Aging to explore the value of a national, independent, nonprofit organization to complement and stimulate federal efforts on Alzheimer's disease. That meeting resulted in the 1980 formation of the Alzheimer's Association with Mr. Stone as founding president. Today, the Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research.

Declaration of National Alzheimer's Disease Month

Awareness of Alzheimer's disease increases, leading Congress to designate November 1983 as the first National Alzheimer's Disease Month.

Beta-amyloid identified

Researchers George Glenner and Cai'ne Wong report identification of "a novel cerebrovascular amyloid protein," known as beta-amyloid — the chief component of Alzheimer's brain plaques and a prime suspect in triggering nerve cell damage.

Nationwide infrastructure for Alzheimer's research established

The NIA begins funding its network of Alzheimer's Disease Centers at flagship medical institutions, establishing a nationwide infrastructure for research, diagnosis and treatment.

Tau protein identified

Researchers discover that tau protein is a key component of tangles — the second pathological hallmark of Alzheimer's disease and another prime suspect in nerve cell degeneration.

First Alzheimer's drug trial

The Alzheimer's Association assists the NIA and Warner-Lambert Pharmaceutical Company (now Pfizer) in launching and recruiting participants for clinical trials of tacrine, the first drug specifically targeting symptoms of Alzheimer's disease.

First deterministic Alzheimer's gene identified

Researchers identify the first gene associated with rare, inherited forms of Alzheimer's disease. This gene on chromosome 21 codes amyloid precursor protein (APP), the parent molecule from which beta-amyloid is formed. Chromosome 21 is also the chromosome of which those with Down syndrome have three copies rather than two. Many individuals with Down syndrome develop Alzheimer's disease, often as young as their 30s and 40s.

Federal clinical study consortium launched

The NIA established the Alzheimer's Disease Cooperative Study (ADCS), a nationwide medical network to facilitate clinical research and conduct federally funded clinical trials.

First Alzheimer's risk factor gene identified

Researchers identify APOE-e4, a form of the apolipoprotein-E (APOE) gene on chromosome 19, as the first gene that raises risk for Alzheimer's but does not determine that a person who has it will develop the disease.

First Alzheimer's drug approved by FDA

The Food and Drug Administration (FDA) approves tacrine (Cognex) as the first drug specifically targeting Alzheimer's memory and thinking symptoms. Four additional drugs are approved over the next 10 years.

President Reagan's diagnosis announced

Former U.S. President Ronald Reagan shares with the American people that he has been diagnosed with Alzheimer's disease. In an open letter to the American people about his decision to share his diagnosis, President Reagan wrote, "In opening our hearts, we hope this might promote greater awareness of this condition. Perhaps it will encourage a clearer understanding of the individuals and families who are affected by it."

First World Alzheimer's Day

The first World Alzheimer's Day (WAD) launches on September 21 by Alzheimer's Disease International, the umbrella organization of Alzheimer's associations.

First transgenic mouse model announced

Researchers announce the first transgenic mouse model that developed Alzheimer-like brain pathology. The mouse was developed by inserting one of the human APP genes linked to a rare, inherited form of Alzheimer's disease. The Alzheimer's Association first awarded a grant to develop a mouse model of a rare neurodegenerative disorder called Gerstmann-Sträussler-Scheinker syndrome in 1989, laying the technical foundation for Alzheimer's mouse models.

"Alzheimer's vaccine" successful in mice

The first in a series of reports is published showing that injecting transgenic "Alzheimer" mice with beta-amyloid prevents the animals from developing plaques and other Alzheimer-like brain changes.

National Alzheimer's Disease Genetics Study begins

The Alzheimer's Association partners with the National Institute on Aging to recruit participants for the National Alzheimer's Disease Genetics Study, a federal initiative to collect and bank blood samples from families with several members who developed Alzheimer's disease late in life in order to identify additional Alzheimer's risk genes.

First report on Pittsburgh Compound B (PIB)

Researchers at the Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) share their first report on an imaging agent called Pittsburgh Compound B (PIB), a major potential breakthrough in disease monitoring and early detection. PIB enters the brain through the bloodstream and attaches itself to beta-amyloid deposits, where it can be detected by positron emission tomography (PET). The Alzheimer's Association provided significant support to initiatives to develop PIB and conduct preclinical testing it in animal studies.

Neuroimaging Initiative (ADNI)

The Alzheimer's Association joins public and private donors as a major sponsor of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a nationwide study to establish standards for obtaining and interpreting brain images. The ultimate goal of ADNI is to determine whether standardized images, possibly combined with laboratory and psychological tests, can identify high-risk individuals; provide early detection; and track and monitor treatment effects, especially in clinical trials of disease-modifying drugs. In 2006, the Association launched the European Alzheimer's Disease Neuroimaging Initiative (E-ADNI), to expand ADNI's scope by combining data from several European brain imaging initiatives with ADNI data. This effort has now grown into World Wide ADNI (WW-ADNI), a global network of flagship research sites united in a common effort to improve diagnosis and speed treatment development with standardized protocols and data shared internationally.

Alzheimer's & Dementia® journal launched

The Alzheimer's Association launches Alzheimer's & Dementia®: The Journal of the Alzheimer's Association to further support a global, interdisciplinary exchange within the Alzheimer's research community.

Healthy Brain Initiative launched

The Alzheimer’s Association and the U.S. Centers for Disease Control and Prevention launch the Healthy Brain Initiative with the publication of A National Public Health Road Map to Maintaining Cognitive Health. The Road Map advances 44 science-based actions emphasizing primary prevention of cognitive impairment. The goal of this initiative is to maintain or improve the cognitive performance of all adults.

International Society to Advance Alzheimer's Research and Treatment formed

To further the work of the global Alzheimer's research community, the Alzheimer's Association creates the International Society to Advance Alzheimer's Research and Treatment (ISTAART), the first and only professional society dedicated to Alzheimer's and dementia.

International Conference on Alzheimer's Disease becomes an annual event

With accelerating progress intensifying the need for global information exchange, the Alzheimer's Association International Conference on Alzheimer's Disease® (AAICAD®) becomes an annual event.

Effort to standardize biomarkers begins

The Alzheimer's Association announces funding of the Alzheimer's Association QC Program for CSF Biomarkers to help overcome variation among institutions in measuring potential biomarkers in cerebrospinal fluid (CSF).

Alzheimer's researchers unite to raise awareness and concern

Dozens of Alzheimer's researchers unite with the Alzheimer's Association for an "Alzheimer's Breakthrough Ride®," a 66-day bike relay across America to raise public and congressional awareness of the urgent need for more federal funding to support the search for effective Alzheimer's treatments.

Alzheimer's clinical trial database established

The Alzheimer's Association and its partners in the Coalition Against Major Diseases (CAMD) released a first-of-its kind database of 4,000 patients who participated in 11 pharmaceutical industry-sponsored clinical trials of Alzheimer's treatments. The combined data, accessible to any qualified researcher, will offer unprecedented power to understand the course of Alzheimer's.

Alzheimer's Association TrialMatch® launched

The Association launches TrialMatch®, a free, easy-to-use clinical studies matching service that connects individuals living with Alzheimer's disease, caregivers, and healthy volunteers with current research studies. Stakeholders unanimously identified building awareness of research studies and increasing enrollment as key strategies to accelerate treatment development.

An influential model of biomarker changes during Alzheimer’s disease progression is first published

A group of researchers publish a working model relating changes in Alzheimer’s biomarkers to disease stage and symptom severity. The model has become a focal point of research into Alzheimer’s biomarkers, and is revised periodically to account for new research.

President Obama signs National Alzheimer's Project Act (NAPA) into law

Groundbreaking legislation establishes our first-ever framework for a national strategic plan to address the Alzheimer's crisis and to coordinate our response on multiple fronts, including research, care and support.

New criteria and guidelines for Alzheimer's disease diagnosis

Three workgroups convened by the Alzheimer's Association and the National Institute on Aging issue updated criteria and guidelines for diagnosing Alzheimer's disease and propose a research agenda to define a new preclinical stage.

Annual assessment for cognitive impairment for all Medicare Beneficiaries implemented as part of Annual Wellness visits

The Centers for Medicare and Medicaid Services implement Annual Wellness Visits for all Medicare Beneficiaries under the Patient Protection and Affordable Care Act. A mandatory part of the Annual Wellness Visit is an assessment for detection of cognitive impairment.

First major clinical trial for prevention of Alzheimer’s disease is initiated

A multinational research consortium, the Dominantly Inherited Alzheimer Network, launches the first major clinical trial testing drug therapy to prevent the onset of Alzheimer’s disease symptoms in people who inherited an autosomal dominant mutation putting them at high risk for the disease.

International Genomics of Alzheimer’s Project (IGAP) researchers identify new genetic risk factors for Alzheimer’s disease

Hundreds of researchers from around the world collaborate to perform a meta-analysis of genome-wide association studies intended to identify genetic variations linked with an increased risk for Alzheimer’s disease. The collaboration revealed 20 genetic variations associated with increased risk, 11 of which had not been linked with Alzheimer’s before. Some of the newly identified genetic variations are thought to be specific to the immune system, adding to mounting evidence of a role for the immune system in Alzheimer’s disease.

Rates of death caused by Alzheimer’s disease found to be much higher than reported on death certificates

Researchers at Rush University find that the annual number of deaths attributable to Alzheimer’s disease in the U.S. among people at least 75 years old is about 500,000, much higher than the number reported on death certificates (>84,000).

Alzheimer's Accountability Act signed into law

The Alzheimer's Association led the fight for this revolutionary law that allows scientists at the NIH to submit an annual research budget directly to Congress.

Historic funding increase

Historic $400 million increase for federal Alzheimer’s disease research funding signed into law, bringing annual funding to $1.4 billion.

Dementia Care Practice Recommendations published

Alzheimer’s Association released Dementia Care Practice Recommendations aimed at helping professional care providers deliver optimal quality, person-centered care for those living with Alzheimer’s and other dementias.

International consortium established to improve care and psychosocial outcomes

The National Institutes of Health (NIH) awarded the Alzheimer’s Association $1.34 million over five years for an international research network, Leveraging an Interdisciplinary Consortium to Improve Care and Outcomes for Persons Living with Alzheimer’s and Dementia (LINC-AD), to improve care and psychosocial outcomes for individuals living with dementia.

Bill Gates helps fund Part the Cloud Research Grant Program

Bill Gates joined the Alzheimer’s Association’s Part the Cloud global research grant program with a $10 million award that will stimulate an additional $20 million in funding to the Alzheimer’s Association.

Alzheimer’s funding reaches all-time high

A $350 million increase for Alzheimer’s and dementia research funding at the National Institutes of Health (NIH) was signed into law, bringing the annual funding to $2.8 billion. An additional $10 million was also approved for the BOLD Infrastructure for Alzheimer’s Act.

Aducanumab approved for treatment of Alzheimer’s disease

Aducanumab (Aduhelm®) received accelerated approval as a treatment for Alzheimer's disease by the U.S. Food and Drug Administration (FDA). This is the first FDA-approved therapy to address the underlying biology of Alzheimer's disease. (Aducanumab will be discontinued on Nov. 1, 2024. Please connect with your provider on treatment options.)

Lecanemab receives traditional approval for treatment of Alzheimer's disease

Lecanemab (Leqembi®) received traditional approval as a treatment for early Alzheimer's from the FDA. It is the first traditionally approved treatment that addresses the underlying biology of Alzheimer's and changes the course of the disease in a meaningful way for people in the early stages.

Donanemab results show drug slows progression of early Alzheimer's

Phase 3 clinical trial results showed that the drug donanemab (which is not yet FDA-approved) significantly slowed cognitive and functional decline in people living with early symptomatic Alzheimer's disease (either mild cognitive impairment or mild dementia).

CMS decides to cover PET imaging for Alzheimer's disease diagnosis

A policy change by the Centers for Medicare & Medicaid Services (CMS) expanded coverage of brain amyloid positron emission tomography (PET) imaging for the diagnosis of Alzheimer's disease, making a valuable tool more accessible across the country.

Alzheimer's Association announces milestone $100 million research investment

The Alzheimer's Association, the world's largest nonprofit funder of Alzheimer's and dementia research, invested a milestone $100 million in research initiatives in 2023, the largest single-year total since the organization's founding in 1980.

Keep Up With Alzheimer’s News and Events

Alzheimer’s Disease Research

What Has Guided Research So Far and Why It Is High Time for a Paradigm Shift

• © 2023
• Christian Behl 0

Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

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• Aims to answer why—after more than 100 years of Alzheimer's research—there is still no convincing therapy available
• Informs on leading perspectives and key developments of Alzheimer's research from its beginnings up until today
• Promotes a paradigm shift in Alzheimer's Disease research and a greater openness towards new disease hypotheses

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Table of contents (21 chapters)

Front matter, introduction.

Christian Behl

The Psychiatrist and Pathologist Aloysius Alzheimer and His Seminal Findings

Alzheimer’s disease research after 1945: the recommencement, alzheimer’s research goes deeper: ultrastructural electron microscopy studies, focus on neurochemistry led to the cholinergic hypothesis of alzheimer’s disease, the glutamatergic hypothesis of alzheimer’s disease, biochemistry and genetics point out a prime suspect for causing alzheimer’s disease, getting to the bottom of it: amyloid beta peptide is derived from a larger precursor, step by step toward an amyloid beta peptide-based hypothesis of alzheimer’s disease, concerns about the amyloid cascade hypothesis and reappraisals, ignorance or conspiracy or just an amyloid firewall that blocks alternative ideas, in the slip stream of amyloid: the tau and tangle hypothesis, focus on tauopathies and beyond, alzheimer’s research gains momentum and spreads out, the amyloid cascade hypothesis has to deliver, finally, beyond app , psen1 , psen2 , and apoe : what else does the genome tell us, alternative hypotheses and observations that were somehow lost on the way, is the persistence of the amyloid cascade hypothesis a result of constant confirmation bias, driving forces of alzheimer’s research directions.

• Alzheimer Clinics
• Alzheimer Therapy
• Alzheimer's Disease
• Amyloid Plaques
• Amyloid-Cascade-Hypothesis
• Agenda Setting
• Aternative Hypotheses
• Risk Factors

About this book

This book highlights the key phases and central findings of Alzheimer’s Disease research since the introduction of the label ‘Alzheimer’s Disease’ in 1910. The author, Christian Behl, puts dementia research in the context of the respective zeitgeist and summarizes the paths that have led to the currently available Alzheimer’s drugs. As the reader is taken through the major developments in Alzheimer's Disease research, particularly over the past thirty years, Behl poses critical questions: Why are the exact causes of Alzheimer's Disease still in the dark, despite all the immense, worldwide research efforts in academia as well as in the pharmaceutical industry? Why has the majority of an entire research field kept focusing on a single hypothesis that establishes the deposition of the amyloid beta peptide in the brain as the key trigger of Alzheimer's pathology, even though this concept has still not been convincingly proven in the clinics? Are there other hypotheses that might explainthe pathogenesis of this complex brain disease, and if so, why were these perspectives not adequately followed?

In this book, Behl tries to answer these questions. Starting with the historical background, the author illustrates the long and arduous research journey, its numerous setbacks, and the many alternative explanations for the disease, which have started gaining increasing attention and acceptance in the Alzheimer’s research community only more recently. 

With his deep dive into the history and progression of this research, including the most recent developments, Behl explains why he believes that it is high time to promote a paradigm shift in Alzheimer’s Disease research.

Authors and Affiliations

About the author.

Christian Behl is Professor of Pathobiochemistry and Director of the Institute of Pathobiochemistry at the University Medical Center of the Johannes Gutenberg University Mainz, Germany. He has been closely following Alzheimer’s Disease research since the early 1990’s, when he first got involved into the field himself during his time at the Salk Institute for Biological Studies, La Jolla, USA. He stayed active in the field all through his research station at the Max Planck Institute of Psychiatry, Munich, Germany, and later in Mainz. There his current research (in Mainz) focuses on the cellular degradation mechanism autophagy in the context of neurodegeneration and aging. For quite some time Behl has been an active advocate for widening the focus of Alzheimer’s Disease research to improve the understanding of this complex, age-related brain disorder. Behl is member of several scientific boards, including the German Alzheimer Foundation.

Bibliographic Information

Book Title : Alzheimer’s Disease Research

Book Subtitle : What Has Guided Research So Far and Why It Is High Time for a Paradigm Shift

Authors : Christian Behl

DOI : https://doi.org/10.1007/978-3-031-31570-1

Publisher : Springer Cham

eBook Packages : Biomedical and Life Sciences , Biomedical and Life Sciences (R0)

Copyright Information : The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023

Hardcover ISBN : 978-3-031-31569-5 Published: 14 July 2023

Softcover ISBN : 978-3-031-31572-5 Due: 14 August 2023

eBook ISBN : 978-3-031-31570-1 Published: 13 July 2023

Edition Number : 1

Number of Pages : XXV, 652

Number of Illustrations : 9 b/w illustrations, 107 illustrations in colour

Topics : Neurosciences , Neurology , Physiology , Cognitive Psychology , Neurosciences , Neurosciences

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Alzheimer's disease drug development pipeline: 2024

Affiliations.

• 1 Chambers-Grundy Center for Transformative Neuroscience Department of Brain Health School of Integrated Health Sciences University of Nevada, Las Vegas (UNLV) Las Vegas Nevada USA.
• 2 Genomic Medicine Institute Lerner Research Institute, Cleveland Clinic Cleveland Ohio USA.
• 3 Howard R Hughes College of Engineering Department of Computer Science University of Nevada, Las Vegas (UNLV) Las Vegas Nevada USA.
• 4 Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland Ohio USA.
• 5 Case Comprehensive Cancer Center Case Western Reserve University School of Medicine Cleveland Ohio USA.
• 6 Cleveland Clinic Genome Center Lerner Research Institute, Cleveland Clinic Cleveland Ohio USA.
• PMID: 38659717
• PMCID: PMC11040692
• DOI: 10.1002/trc2.12465

Introduction: New therapies to prevent or delay the onset of symptoms, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Methods: We interrogated clinicaltrials.gov including all clinical trials assessing pharmaceutical therapies for AD active in on January 1, 2024. We used the Common Alzheimer's Disease Research Ontology (CADRO) to classify the targets of therapies in the pipeline.

Results: There are 164 trials assessing 127 drugs across the 2024 AD pipeline. There were 48 trials in Phase 3 testing 32 drugs, 90 trials in Phase 2 assessing 81 drugs, and 26 trials in Phase 1 testing 25 agents. Of the 164 trials, 34% ( N = 56) assess disease-modifying biological agents, 41% ( N = 68) test disease-modifying small molecule drugs, 10% ( N = 17) evaluate cognitive enhancing agents, and 14% ( N = 23) test drugs for the treatment of neuropsychiatric symptoms.

Discussion: Compared to the 2023 pipeline, there are fewer trials (164 vs. 187), fewer drugs (127 vs. 141), fewer new chemical entities (88 vs. 101), and a similar number of repurposed agents (39 vs. 40).

Highlights: In the 2024 Alzheimer's disease drug development pipeline, there are 164 clinical trials assessing 127 drugs.The 2024 Alzheimer's disease drug development pipeline has contracted compared to the 2023 Alzheimer pipeline with fewer trials, fewer drugs, and fewer new chemical entities.Drugs in the Alzheimer's disease drug development pipeline target a wide array of targets; the most common processes targeted include neurotransmitter receptors, inflammation, amyloid, and synaptic plasticity.The total development time for a potential Alzheimer's disease therapy to progress from nonclinical studies to FDA review is approximately 13 years.

© 2024 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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• Published: 13 May 2021

Alzheimer disease

• David S. Knopman   ORCID: orcid.org/0000-0002-6544-066X 1 ,
• Helene Amieva 2 ,
• Ronald C. Petersen 1 ,
• Gäel Chételat 3 ,
• David M. Holtzman 4 ,
• Bradley T. Hyman   ORCID: orcid.org/0000-0002-7959-9401 5 ,
• Ralph A. Nixon 6 , 7 &
• David T. Jones   ORCID: orcid.org/0000-0002-4807-9833 1  

Nature Reviews Disease Primers volume  7 , Article number:  33 ( 2021 ) Cite this article

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• Alzheimer's disease
• Diagnostic markers
• Translational research

Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic neurodegenerative disease that causes an amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants. AD is a common cause of cognitive impairment acquired in midlife and late-life but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. This Primer conceives of AD biology as the brain disorder that results from a complex interplay of loss of synaptic homeostasis and dysfunction in the highly interrelated endosomal/lysosomal clearance pathways in which the precursors, aggregated species and post-translationally modified products of Aβ and tau play important roles. Therapeutic endeavours are still struggling to find targets within this framework that substantially change the clinical course in persons with AD.

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Acknowledgements

The authors acknowledge research support from NIH (D.S.K. and R.C.P, P30 AG062677 and U01 AG006786; B.T.H., P30AG062421; R.A.N. P01 AG017617 and R01 AG062376).

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David S. Knopman, Ronald C. Petersen & David T. Jones

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Helene Amieva

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Gäel Chételat

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

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Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

Bradley T. Hyman

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Introduction (D.S.K.); Epidemiology (H.A.); Mechanisms/pathophysiology (D.T.J., R.A.N., B.T.H. and D.M.H.); Diagnosis, screening and prevention (G.C., R.C.P. and D.S.K.); Management (R.C.P. and D.S.K.); Quality of life (D.S.K.); Outlook (D.S.K.); Overview of Primer (D.S.K.).

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Competing interests.

D.S.K. served on a Data Safety Monitoring Board for the DIAN study. He serves on a Data Safety Monitoring Board for a tau therapeutic for Biogen but receives no personal compensation. He is a site investigator in a Biogen aducanumab trial. He is an investigator in a clinical trial sponsored by Lilly Pharmaceuticals and the University of Southern California. He serves as a consultant for Samus Therapeutics, Third Rock, Roche and Alzeca Biosciences but receives no personal compensation. He receives research support from the NIH. G.C. serves on the Scientific Advisory Board of the Fondation Vaincre Alzheimer but receives no personal compensation. She receives personal fees from Fondation d’entreprise MMA des Entrepreneurs du Futur and from Fondation Alzheimer as she serves in the Operational Committee. She receives research support from European Union Horizon 2020 research and innovation programme (grant agreement number 667696), Inserm, Fondation d’entreprise MMA des Entrepreneurs du Futur, Fondation Alzheimer, Programme Hospitalier de Recherche Clinique, Région Normandie, Association France Alzheimer et maladies apparentées and Fondation Vaincre Alzheimer. R.C.P. is a consultant for Biogen, Inc., Roche, Inc., Merck, Inc., Genentech Inc. and Eisai, Inc., has given educational lectures for GE Healthcare, receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003), UpToDate, and receives research support from the NIH. B.T.H. has a family member who works at Novartis and owns stock in Novartis; he serves on the SAB of Dewpoint and owns stock. He serves on a scientific advisory board or is a consultant for Biogen, Novartis, Cell Signalling, the US Dept of Justice, Takeda, Vigil, W20 group and Seer. His laboratory is supported by sponsored research agreements with Abbvie, F Prim, and research grants from the National Institutes of Health, Cure Alzheimer’s Fund, Tau Consortium, Brightfocus and the JPB Foundation. H.A. serves on the Scientific Advisory Board of the Observatoire des Mémoires but receives no personal compensation. She receives research support from Spoelberch Foundation, Association France Alzheimer et maladies apparentées, the Regional Health Agency of Aquitaine and National Research Agency. D.M.H. reports being a Co-founder for C2N Diagnostics LLC and participating in scientific advisory boards/consulting for Genentech, C2N Diagnostics, Denali, Merck and Idorsia. He is an inventor on patents licensed by Washington University to C2N Diagnostics on the therapeutic use of anti-tau antibodies (this anti-tau antibody programme is licensed to Abbvie) and to Eli Lilly on the therapeutic use of an anti-amyloid-β antibody. His laboratory receives research grants from the National Institutes of Health, Cure Alzheimer’s Fund, Tau Consortium, the JPB Foundation, Good Ventures, Centene, BrightFocus and C2N Diagnostics. All other authors declare no competing interests.

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Knopman, D.S., Amieva, H., Petersen, R.C. et al. Alzheimer disease. Nat Rev Dis Primers 7 , 33 (2021). https://doi.org/10.1038/s41572-021-00269-y

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Researchers discover the mechanism that links a diet rich in fats with Alzheimer's disease

by University of Rovira i Virgili

A study led by the Universitat Rovira i Virgili (URV) has revealed the mechanism behind the link between a diet high in saturated fats and Alzheimer's disease. The research focused on how this kind of diet affects certain molecules found in the blood and in other tissues such as the brain that act as markers and regulators of the disease.

The study was headed by Mònica Bulló, professor at the Department of Biochemistry and Biotechnology and member of the Metabolic Health and Nutrition unit and the Environmental, Food and Toxicological Technology Centre (TecnATox) of the URV, in collaboration with the Pere Virgili Health Research Institute (IISPV), CIBERobn and the University of Barcelona. The results have been published in the journal Nutrients .

The research was conducted on mice models who developed Alzheimer's disease in adulthood. Previous studies in these animals had already shown that after a diet high in saturated fats the mice developed Alzheimer's much earlier than mice on a conventional diet. However, the mechanisms that led to the onset of Alzheimer's remained unknown. That is, until now.

The researchers analyzed the expression of 15 miRNAs, small molecules of RNA that play a crucial role in genetic regulation in both plasma and brain tissues. The team examined changes in insulin-related miRNAs in mouse models predisposed to Alzheimer's not on a diet low in saturated fats.

The results demonstrated that their metabolism worsened after being on this diet for six months: their body weight increased significantly and their response to glucose and insulin decreased. These same characteristics can also be found in people with obesity or type 2 diabetes.

Furthermore, researchers found changes to various miRNAs in both the blood and the brain. These changes were related to processes that can cause brain damage , such as the accumulation of β-amyloid plaques (protein deposits that form in the brain and which are markers of Alzheimer's), excessive production of the tau protein (which can damage brain cells when it gets out of control) and inflammation in the brain.

"The results of this study are a step forward in our understanding of this disease and may explain the relationship between obesity, type 2 diabetes and the onset of Alzheimer's. The findings also offer new targets for the possible prevention and treatment of the disease," said researcher Bulló.

The study not only provides new data on how a high-fat diet can affect the health of the brain, but also opens the door to future research into dietary strategies as a means of treating Alzheimer's. The results underline the importance of a balanced diet in preventing neurodegenerative diseases and highlight miRNAs as targets for therapeutic interventions.

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Alzheimer's drug adoption in US slowed by doctors' skepticism

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Reporting by Julie Steenhuysen in Chicago; editing by Caroline Humer and Suzanne Goldenberg

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GSK raises full-year profit forecast, says first-half will see stronger sales

GSK raised its full-year profit forecast on Wednesday and said its sales would be higher in the first six months of the year than the second half on the back of strong demand for its common respiratory virus and shingles vaccines.