Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

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

Published: Thursday, March 01, 2012
Last Updated: Thursday, March 01, 2012
Bookmark and Share
A repression of gene activity in the brain appears to be an early event affecting people with Alzheimer's disease. 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.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Predicting Effective Drug Combinations For TB
Researchers analyzed gene regulatory networks to explain the effectiveness of an experimental drug combination against drug-resistant tuberculosis bacteria.
Wednesday, June 15, 2016
Genomic Data Commons Launched
Part of the National Cancer Moonshot, the GDC will centralize and standardize accessible data.
Tuesday, June 07, 2016
Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
NIH Funds New Studies on Ethical, Legal and Social Impact of Genomic Information
Four new grants from the National Institutes of Health will support research on the ethical, legal and social questions raised by advances in genomics research and the increasing availability of genomic information.
Wednesday, May 18, 2016
Researchers Identify Genetic Links to Educational Attainment
Researchers at NIH have suggested that the large genetics analyses may be able to help discover biological pathways as well.
Thursday, May 12, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
NIH Sequences Genome of a Fungus
Researchers at the Institute have sequenced genome of human, mouse and rat Pneumocystis that cause life-threatening Pneumonia in immunosuppressed hosts.
Tuesday, April 12, 2016
Decoding Ties Between Vascular Disease, Alzheimer’s
NIH consortium uses big data, team science to uncover complex interplay of factors.
Tuesday, March 15, 2016
Researchers Find Link Between Death of Tumor-Support Cells and Cancer Metastasis
Researchers at NIH have found that the lifespan of supportive cells in a tumor may control the spread of cancer.
Tuesday, February 23, 2016
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH-funded study could lead to new tick control methods.
Tuesday, February 09, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Thursday, February 04, 2016
Genome-Wide Study Yields Markers of Lithium Response
An international consortium of scientists has identified a stretch of chromosome that is associated with responsiveness to the mood-stabilizing medication lithium among patients with bipolar disorder.
Monday, February 01, 2016
Schizophrenia’s Strongest Known Genetic Risk Deconstructed
Suspect gene may trigger runaway synaptic pruning during adolescence – NIH-funded study.
Thursday, January 28, 2016
NIH Genome Sequencing Program Targets the Genomic Bases of Common, Rare Disease
The National Institutes of Health will fund a set of genome sequencing and analysis centers whose research will focus on understanding the genomic bases of common and rare human diseases.
Friday, January 15, 2016
Scientific News
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Fix for 3-Billion-Year-Old Genetic Error
Researchers at The University of Texas at Austin have developed a fix that allows RNA to accurately proofread for the first time.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Revealing the Genetic Causes of Bowel Cancer
A landmark study has given the most detailed picture yet of the genetics of bowel cancer — the UK's fourth most common cancer.
The Epigenetic Influences of Chronic Pain
Researchers at Drexel University College of Medicine are aiming to identify new molecular mechanisms involved in pain.
Fighting Resistant Blood Cancer Cells
Biologists present new findings on chronic myeloid leukemia and possible therapeutic approaches.
Tumor Cells Develop Predictable Characteristics
Scientists have discovered that cancer cells at the edge of a tumor that are close to the surrounding environment are predictably different from the cells within the interior of the tumor.
Mothers Obesity Could be Passed on in mtDNA
Obesity can predispose offspring in multiple generations to metabolic problems.
New Imaging Method Reveals Nanoscale Details about DNA
Enhancement to super-resolution microscopy shows orientation of individual molecules, providing a new window into DNA’s structure and dynamics.
Genetic Research Can Significantly Improve Drug Development
With drug development costs topping $1.2bn (£850 million) to get a single treatment to the point it can be sold and used in the clinic, could genetic analysis save hundreds of millions of dollars?
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!