Skip to main content
  • U.S. Department of Health & Human Services
National Institutes of Health (NIH) - Turning Discovery into Health
  • Virtual Tour
  • En Español

Site Menu

  • Home
  • Health Information
    • Health Care Providers & Facilities
    • Health Info Lines
    • HealthCare.gov
    • Science Education Resources
    • NIH Clinical Research Trials and You
    • Talking to Your Doctor

    More »

    Quick Links

    • MedlinePlus Health Info
    • NIH News in Health
    • Wellness Toolkits
  • Grants & Funding
    • Grants Home Page
    • Find Funding
    • Due Dates
    • How to Apply
    • About Grants
    • Policy & Compliance
    • Grants News/Blog
    • Contracts
    • Loan Repayment

    More »

    Quick Links

    • RePORT
    • eRA Commons
    • NIH Common Fund
  • News & Events
    • News Releases
    • Digital Media Kits
    • Media Resources
    • Media Contacts
    • Images and B-roll
    • Events
    • Social Media

    More »

    Quick Links

    • NIH News in Health
    • NIH Research Matters
    • NIH Record
  • Research & Training
    • Medical Research Initiatives
    • Science Highlights
    • Science Education
    • Research in NIH Labs & Clinics
    • Training Opportunities
    • Library Resources
    • Research Resources
    • Clinical Research Resources
    • Safety, Regulation and Guidance

    More »

    Quick Links

    • PubMed
    • Stem Cell Information
    • OppNet
    • NIDB
    • NIH Blueprint for Neuroscience Research
  • Institutes at NIH
    • List of Institutes and Centers
    • NIH Office of the Director
    • Directors of NIH Institutes and Centers
    • NIH Institute and Center Contact Information

    More »

    Quick Links

    • NCI
    • NEI
    • NHLBI
    • NHGRI
    • NIA
    • NIAAA
    • NIAID
    • NIAMS
    • NIBIB
    • NICHD
    • NIDCD
    • NIDCR
    • NIDDK
    • NIDA
    • NIEHS
    • NIGMS
    • NIMH
    • NIMHD
    • NINDS
    • NINR
    • NLM
    • CC
    • CIT
    • CSR
    • FIC
    • NCATS
    • NCCIH
  • About NIH
    • Who We Are
    • What We Do
    • Jobs at NIH
    • Visitor Information
    • Frequently Asked Questions
    • Contact Us

    More »

    Quick Links

    • The NIH Director
    • Take the Virtual Tour
    • NIH…Turning Discovery Into Health®
    • Impact of NIH Research
    • Science, Health, and Public Trust

You are here

Home » News & Events » News Releases

News Releases

News Release

Wednesday, February 29, 2012

Blockade of Learning and Memory Genes may Occur Early in Alzheimer’s Disease

NIH-funded research could lead to new therapy.

Mouse model of Alzheimer's disease elevated protein levels in the hippocampus. In a mouse model of Alzheimer's disease (right), HDAC2 levels in the hippocampus are higher than in the normal mouse hippocampus (left) Dr. Li-Huei Tsai, Massachusetts Institute of Technology

A repression of gene activity in the brain appears to be an early event affecting people with Alzheimer's disease, researchers funded by the National Institutes of Health have found. In mouse models of Alzheimer's disease, this epigenetic blockade and its effects on memory were treatable.

"These findings provide a glimpse of the brain shutting down the ability to form new memories gene by gene in Alzheimer's disease, and offer hope that we may be able to counteract this process," said Roderick Corriveau, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS), which helped fund the research.

The study was led by Li-Huei Tsai, Ph.D., who is director of The Picower Institute for Learning and Memory at the Massachusetts Institute of Technology and an investigator at the Howard Hughes Medical Institute. It was published online February 29 in Nature.

Dr. Tsai and her team found that a protein called histone deacetylase 2 (HDAC2) accumulates in the brain early in the course of Alzheimer's disease in mouse models and in people with the disease. HDAC2 is known to tighten up spools of DNA, effectively locking down the genes within and reducing their activity, or expression.

In the mice, the increase in HDAC2 appears to produce a blockade of genes involved in learning and memory. Preventing the build-up of HDAC2 protected the mice from memory loss.

Dr. Tsai and her team examined two mouse models of Alzheimer's around the time that the mice begin to show signs of brain cell degeneration. They found that the mice had higher levels of HDAC2, but not other related HDAC proteins, specifically in the parts of the brain involved in learning and memory. This increase in HDAC2 was associated with a decrease in the expression of neuronal genes that HDAC2 is known to regulate.

Use of a gene therapy approach to reduce the levels of HDAC2 prevented the blockade of gene expression. The treatment also prevented learning and memory impairments in the mice. It did not prevent neuronal death, but it did enhance neuroplasticity — the ability of neurons to form new connections.

Dr. Tsai and her team also examined HDAC2 levels in autopsied brain tissue from 19 people with Alzheimer’s at different stages of the disease, and from seven unaffected individuals. Even in its earliest stages, the disease was associated with higher HDAC2 levels in the learning and memory regions of the brain.

"We think that the blockade of gene expression plays a very important role in the cognitive decline associated with Alzheimer's disease," said Dr. Tsai. "The good news is that the blockade is potentially reversible."

Alzheimer's disease is the most common cause of dementia in older adults, and affects as many as 5.1 million Americans. In the most common type of Alzheimer's disease, symptoms usually appear after age 65. A hallmark of the disease is the accumulation of a toxic protein fragment called beta-amyloid in brain cells, which is widely believed to be the initial trigger for neurodegeneration.

Dr. Tsai theorizes that HDAC2 is brought into play by beta-amyloid. Indeed, she and her team found that exposing mouse neurons to beta-amyloid caused them to produce more HDAC2.

"We think beta-amyloid triggers a cascade of damaging reactions. Once of these is to activate HDAC2, which in turn blocks the expression of genes needed for brain plasticity. Once this blockade is in place, it may have a more systemic, chronic effect on the brain," she said.

Vaccines and other therapies aimed at reducing beta-amyloid are in clinical trials. Efforts to reduce HDAC2 may provide a complementary approach to treating Alzheimer's, Dr. Tsai said. She has previously reported that HDAC inhibitor compounds can protect against signs of Alzheimer's disease in mice. A problem with such compounds is that they inhibit not only HDAC2 but related HDAC proteins, leading to broad and potentially toxic effects. The new study supports the possibility of developing drugs more specifically targeted to HDAC2 and the pathology of Alzheimer’s disease, Dr. Tsai said. Her team is working to identify HDAC2-specific inhibitors that could be developed into drugs and moved into trials.

Dr. Tsai's study was supported by NINDS and the National Institute on Aging through the NIH Common Fund Epigenomics Program. Additional support was provided through the NIH Blueprint for Neuroscience Research and its Neuroplasticity initiative.

NINDS is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease — a burden borne by every age group, by every segment of society, by people all over the world.

NIA leads the federal government effort conducting and supporting research on aging and the health and well-being of older people. NIA provides information on age-related cognitive change and neurodegenerative disease specifically at its Alzheimer's Disease Education and Referral (ADEAR) Center at www.nia.nih.gov/Alzheimers.

The NIH Common Fund Epigenomics Program aims to generate new research tools, technologies, datasets, and infrastructure to accelerate the understanding of how genome-wide chemical modifications to DNA regulate gene activity and what role these modifications play in health and disease.

The NIH Blueprint for Neuroscience Research is a cooperative effort among the NIH Office of the Director and the 15 NIH Institutes and Centers that support research on the nervous system. By pooling resources and expertise, the Blueprint supports transformative neuroscience research, and the development of new tools, training opportunities, and other resources to assist neuroscientists. For information about the Blueprint's Neuroplasticity initiative, visit http://www.neuroscienceblueprint.nih.gov/blueprint_basics/BP_themes.htm.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

###

Institute/Center

National Institute of Neurological Disorders and Stroke (NINDS)

Contact

Daniel Stimson
301-496-5751

Connect with Us

  • Subscribe to news releases
  • RSS Feed

Connect with Us

  • Contact Us
  • X
  • Facebook
  • Instagram
  • YouTube
  • Flickr
  • More Social Media from NIH

Footer

  • NIH Home
  • Virtual Tour
  • En Español
  • Visitor Information
  • Frequently Asked Questions
  • Privacy Policy
  • Disclaimers
  • Accessibility
  • NIH Website Archives
  • Nondiscrimination Notice
  • Freedom of Information Act
  • No Fear Act
  • HHS Vulnerability Disclosure
  • Office of Inspector General
  • USA.gov

NIH…Turning Discovery Into Health®

National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892

U.S. Department of Health and Human Services

Back to Top