ProHealth health Vitamin and Natural Supplement Store and Health
Home  |  Log In  |  My Account  |  View Cart  View Your ProHealth Vitamin and Supplement Shopping Cart
800-366-6056  |  Contact Us  |  Help
Facebook Google Plus
Fibromyalgia  Chronic Fatigue Syndrome & M.E.  Lyme Disease  Natural Wellness  Supplement News  Forums  Our Story
Store     Brands   |   A-Z Index   |   Best Sellers   |   New Products   |   Deals & Specials   |   Under $10   |   SmartSavings Club

Trending News

Meta-analysis adds evidence to association between omega-3 supplementation and lower heart rate

Friendly User's Guide for the Timing of Nutritional Supplements

The Health Benefits of Manuka Honey

Increase Your Magnesium Intake

Love Your Lungs With Tomatoes and Apples

Top Tips to Boost Your Immunity

Essential Oils Lower Blood Pressure

Vitamin D supplementation could ease IBS symptoms

11 Amazing Health Benefits of Using Baking Soda

Nicotinamide riboside shows promise for treatment of Alzheimer’s disease

Print Page
Email Article

New Alzheimer's-Associated Mutation May Provide Key To Disease Process

  [ Not Yet Rated ]   [ Discuss This Article ]
By Press Release by the Massachusetts Gen Hosp • • July 22, 1998

Researchers from the Massachusetts General Hospital (MGH) and colleagues at the Harvard School of Public Health (HSPH) and other institutions have identified a new gene mutation strongly associated with the risk of developing late-onset Alzheimer's disease, the most common form of the brain disorder. Most significantly, the protein coded for by this gene -- known as alpha-2 macroglobulin (A2M) -- interacts with proteins coded by other Alzheimer's-associated genes, suggesting a process that could be key in the disease's development.

"This finding leads us directly to a protein pathway that we think drives the Alzheimer's disease process," says Rudolph Tanzi, Ph.D., director of the MGH Genetics and Aging Unit and senior author of the report, appearing in the August issue of Nature Genetics. "It could be a powerful new target for the development of drugs to prevent or treat this disease." Tanzi and his colleagues stress that the new mutation is not appropriate for use in diagnosing or predicting Alzheimer's disease. The data also are being presented July 22 in Amsterdam at the Sixth International Conference on Alzheimer's Disease and Related Disorders.

Steven Moldin, Ph.D., acting chief of the NIMH Genetics Research Branch says, "If replicated, this would prove to be a very major finding in understanding the genetic basis of the common, late-onset form of Alzheimer's disease."

Scientists have long been familiar with the A2M protein and its gene, found on chromosome 12. A2M is a protease inhibitor, controlling the activity of enzymes that break down other proteins, and has been known to interact with a nerve cell receptor called LRP (low-density lipoprotein receptor-related protein). Two important clues led Tanzi and his colleagues to examine whether mutations in A2M might be associated with Alzheimer's risk. First, two proteins known to be involved with Alzheimer's -- the amyloid precursor protein and apoE -- also interact with LRP. Second, cell culture studies have shown that A2M tightly binds the protein fragment A-beta, the major component of the amyloid plaques found in the brains of Alzheimer's patients. Those studies showed that A2M facilitates the breakdown and removal of A-beta from brain cells -- one of the processes that, when it goes wrong, are believed to underlie Alzheimer's.

Following these clues, the MGH-led team looked for associations between mutations in A2M and Alzheimer's using the National Institute of Mental Health (NIMH) Genetics Initiative AD sample, a collection of DNA samples and clinical information from hundreds of families in which more than one individual has Alzheimer's. Employing new family-based association methods -- tools that identify disease genes based on differences observed within families -- they found that a particular gene mutation called A2M-2, in which part of the gene is missing, was strongly associated with Alzheimer's. The family-based association tool used in this study was developed by the HSPH team members.

Deborah Blacker, MD, ScD, of the MGH, the paper's lead author, says, "Alzheimer's is proving to be a very genetically complex disease in which many factors interact to determine who will be affected. In addition to what it may tell us about the disease process, this finding -- if replicated -- will help us sort out the role of additional genetic and environment factors in future studies."

Tanzi explains that the addition of this new piece to the Alzheimer's puzzle suggests a picture of how the disease may develop. "There is little question now that the key event triggering Alzheimer's is the deposition of amyloid plaques, toxic deposits of insoluble A-beta protein fragments, inside the brain. It could be that the A2M, apoE and LRP proteins are involved in a very sensitive, balanced system that breaks down A-beta and harmlessly removes it from brain cells.

"We have a theory that LRP sits in the synapses, the junctions where brain cells communicate with each other, and works with A2M to keep A-beta from accumulating," he continues. "If a defective A2M kept the system from working properly, or if a variant of apoE blocked the usual breakdown process, A-beta plaques could form and clog the synapses -- both slowing nerve signals and preventing the release of growth factors that keep cells healthy. Finding a way to mimic the normal function of A2M with a drug could give us a powerful therapeutic tool."

The level of risk conferred by the A2M-2 mutation appears similar to the risk conferred by the gene variant apoE-4. However, individuals carrying both variants do not seem to have a further increase in their risk. Although apoE appears to affect the age at which symptoms appear, the researchers found that A2M-2 does not affect age of onset. As with apoE-4, the presence or absence of the A2M-2 mutation cannot confirm or rule out whether someone has or will develop Alzheimer's. The researchers also noted that the area of chromosome 12 where the A2M gene is found is not the same area identified as harboring an Alzheimer's disease marker in a 1997 study from Duke University. The MGH team was unable to confirm that finding.

Tanzi and Blacker's co-authors on the Nature Genetics paper are Linda Rodes, Marilyn Albert, Ph.D., and Bradley Hyman, MD, Ph.D., of the MGH; Marsha Wilcox, EdD, Nan Laird Ph.D., and Steven Horvath, Ph.D., of the Harvard School of Public Health; Rodney Go, Ph.D., Rodney Perry, Ph.D., and Bracie Watson, Ph.D., of the University of Alabama at Birmingham; and Susan Bassett, Ph.D., and Melvin McInnis, MD, of Johns Hopkins University Medical Institutions. This study was supported by grants from the National Institute of Mental Health, and Tanzi's team also receives support from the National Institute on Aging, the Alzheimer's Association and the American Health Assistance Foundation.

Source: Massachusetts General Hospital Press Release: July 22, 1998

Contact: Susan McGreevey,, 617-724-2764

Post a Comment

Featured Products From the ProHealth Store
FibroSleep™ Energy NADH™ 12.5mg Ultra ATP+, Double Strength

Article Comments

Be the first to comment on this article!

Post a Comment

Optimized Curcumin Longvida with Omega-3

Featured Products

FibroSleep™ FibroSleep™
The All-in-One Natural Sleep Aid
Mitochondria Ignite™ with NT Factor® Mitochondria Ignite™ with NT Factor®
Reduce Fatigue up to 45%
Optimized Curcumin Longvida® Optimized Curcumin Longvida®
Supports Cognition, Memory & Overall Health
Ultra EPA  - Fish Oil Ultra EPA - Fish Oil
Ultra concentrated source of essential fish oils

Natural Remedies

Coenzyme Q10 - The Energy Maker Coenzyme Q10 - The Energy Maker
The Crucial Role CoQ10 Plays in Fibromyalgia and ME/CFS The Crucial Role CoQ10 Plays in Fibromyalgia and ME/CFS
Astaxanthin - A Little-Known but Power-Packed Nutrient Astaxanthin - A Little-Known but Power-Packed Nutrient
Looking for Energy? Turn to Plants. Looking for Energy? Turn to Plants.
Probiotic Mint Promotes Healthy Gums & Teeth, Freshens Breath and Whitens Teeth Probiotic Mint Promotes Healthy Gums & Teeth, Freshens Breath and Whitens Teeth

ProHealth, Inc.
555 Maple Ave
Carpinteria, CA 93013
(800) 366-6056  |  Email

· Become a Wholesaler
· Vendor Inquiries
· Affiliate Program
Credit Card Processing
Get the latest news about Fibromyalgia, M.E/Chronic Fatigue Syndrome, Lyme Disease and Natural Wellness

CONNECT WITH US ProHealth on Facebook  ProHealth on Twitter  ProHealth on Pinterest  ProHealth on Google Plus

© 2018 ProHealth, Inc. All rights reserved. Pain Tracker App  |  Store  |  Customer Service  |  Guarantee  |  Privacy  |  Contact Us  |  Library  |  RSS  |  Site Map