Activate Now
 
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

Patient Insights into the Design of Technology to Support a Strengths-Based Approach to Health Care.

Greater intake of dietary omega-3 fatty acids associated with lower risk of diabetic retinopathy

SURVEY: Weight Management & Chronic Illness

Japanese green tea consumers have reduced risk of dementia

Do Nothing, Accomplish Everything! The Connection Between Breathing and Healing

Nature Heals

Best Herbs to Help With Insomnia

Meet the ProHealth Editors

Choline: Why You Should Eat Your Egg Yolks and Take Krill

Calcium, vitamin D supplementation associated improved stroke recovery

 
Print Page
Email Article

SURPRISE: Alzheimer’s plaques start in liver & migrate to brain, Scripps Research suggests

  [ 25 votes ]   [ Discuss This Article ]
www.ProHealth.com • March 3, 2011


Unexpected results from a study by gene researchers at Scripps Research Institute and ModGene, LLC could completely alter scientists' ideas about Alzheimer's disease - indicating that the liver, not the brain, may be the source of the "amyloid" that deposits as brain plaques associated with Alzheimer’s disease, and potentially simplifying the nature of treatment & prevention strategies.

These unexpected results, from a study at the Scripps Research Institute and ModGene LLC, were published Mar 3 by The Journal of Neuroscience Research. [See “Peripheral reduction of Beta-amyloid is sufficient to reduce brain Beta-Amyloid: Implications for Alzheimer’s disease.”]

Genetic Links to Amyloid Levels

In the study, the scientists used a mouse model for Alzheimer's disease to identify genes that influence the amount of amyloid that accumulates in the brain.

They found three genes that protected mice from brain amyloid accumulation and deposition. For each gene, lower expression in the liver protected the mouse brain.

One of the genes encodes presenilin - a cell membrane protein believed to contribute to the development of human Alzheimer's.

"This unexpected finding holds promise for the development of new therapies to fight Alzheimer's," said Scripps molecular neurobiologist Prof. J. Greg Sutcliffe, who led the study. "This could greatly simplify the challenge of developing therapies and prevention."

An estimated 5.1 million Americans have Alzheimer's disease, including nearly half of people age 85 and older.

By 2050, the number of people age 65 and over with this disease will range from 11 million to 16 million unless science finds a way to prevent or effectively treat it. In addition to the human misery caused by the disease, there is the unfathomable cost.

A new report from the Alzheimer's Association shows that in the absence of disease-modifying treatments, the cumulative costs of care for people with Alzheimer's from 2010 to 2050 will exceed $20 trillion.

A Genetic Search-and-Find Mission

In trying to help solve the Alzheimer's puzzle, in the past few years Sutcliffe and his collaborators have focused their research on naturally occurring, inherited differences in neurological disease susceptibility among different mouse strains, creating extensive databases cataloging gene activity in different tissues, as measured by mRNA accumulation.

These data offer up maps of trait expression that can be superimposed on maps of disease modifier genes.

As is the case with nearly all scientific discovery, Sutcliffe's research builds on previous findings.

• Several years ago, researchers at Case Western Reserve mapped three genes that modify the accumulation of pathological beta amyloid in the brains of a transgenic mouse model of Alzheimer's disease to large chromosomal regions, each containing hundreds of genes. The Case Western scientists used crosses between the B6 and D2 strains of mice, studying more than 500 progeny.

• Using the results from this study, Sutcliffe turned his databases of gene expression to the mouse model of Alzheimer's, looking for differences in gene expression that correlated with differences in disease susceptibility between the B6 and D2 strains.

This intensive work involved writing computer programs that identified each genetic difference that distinguished the B6 and D2 genomes, then running mathematical correlation analysis (known as regression analysis) of each difference. Correlations were made between the genotype differences (B6 or D2) and the amount of mRNA product made from each of the more than 25,000 genes in a particular tissue in the 40 recombinant inbred mouse strains.

These correlations were repeated 10 times to cover 10 tissues, the liver being one of them.

"A key aspect of this work was learning how to ask questions of massive data sets to glean information about the identities of heritable modifier genes," Sutcliffe said.

"This was novel and, in a sense, groundbreaking work: We were inventing a new way to identify modifier genes, putting all of these steps together and automating the process.

“We realized we could learn about how a transgene's pathogenic effect was being modified without studying the transgenic mice ourselves."

Looking for a Few Good Candidates

Sutcliffe's gene hunt offered up good matches, candidates, for each of the three disease modifier genes discovered by the Case Western scientists, and one of these candidates - the mouse gene corresponding to a gene known to predispose humans carrying particular variations of it to develop early-onset Alzheimer's disease - was of special interest to his team.

"The product of that gene, called Presenilin2, is part of an enzyme complex involved in the generation of pathogenic beta amyloid," Sutcliffe explained. "Unexpectedly, heritable expression of Presenilin2 was found in the liver but not in the brain. Higher expression of Presenilin2 in the liver correlated with greater accumulation of beta amyloid in the brain and development of Alzheimer's-like pathology."

This finding suggested that significant concentrations of beta amyloid might originate in the liver, circulate in the blood, and enter the brain. If true, blocking production of beta amyloid in the liver should protect the brain.

To test this hypothesis, Sutcliffe's team set up an in vivo experiment using wild-type mice since they would most closely replicate the natural beta amyloid-producing environment.

"We reasoned that if brain amyloid was being born in the liver and transported to the brain by the blood, then that should be the case in all mice," Sutcliffe said, "and one would predict in humans, too."

The mice were administered imatinib (trade name Gleevec, an FDA-approved cancer drug), a relatively new drug currently approved for treatment of chronic myelogenous leukemia and gastrointestinal tumors.

The drug potently reduces the production of beta amyloid in neuroblastoma cells transfected by amyloid precursor protein (APP) and also in cell-free extracts prepared from the transfected cells.

Importantly, Gleevec has poor penetration of the blood-brain barrier in both mice and humans.

"This characteristic of the drug is precisely why we chose to use it," Sutcliffe explained. "Because it doesn't penetrate the blood-brain barrier, we were able to focus on the production of amyloid outside of the brain and how that production might contribute to amyloid that accumulates in the brain, where it is associated with disease."

The mice were injected with Gleevec twice a day for seven days; then plasma and brain tissue were collected, and the amount of beta amyloid in the blood and brain was measured.

The findings: The drug dramatically reduced beta amyloid not only in the blood, but also in the brain where the drug cannot penetrate.

Thus, an appreciable portion of brain amyloid must originate outside of the brain, and imatinib represents a candidate for preventing and treating Alzheimer's.

As for the future of this research, Sutcliffe says he hopes to find a partner and investors to move the work into clinical trials and new drug development.

Source: Scripps Research Institute, Mar 3, 2011




Post a Comment

Featured Products From the ProHealth Store
Energy NADH™ 12.5mg Ultra EPA  - Fish Oil Ultra ATP+, Double Strength

Looking for Vitamins, Herbs and Supplements?
Search the ProHealth Store for Hundreds of Natural Health Products


Article Comments



Be the first to comment on this article!

Post a Comment


 
Natural Pain Relief Supplements

Featured Products

Optimized Curcumin Longvida® Optimized Curcumin Longvida®
Supports Cognition, Memory & Overall Health
Energy NADH™ 12.5mg Energy NADH™ 12.5mg
Improve Energy & Cognitive Function
FibroSleep™ FibroSleep™
The All-in-One Natural Sleep Aid
Ultra EPA  - Fish Oil Ultra EPA - Fish Oil
Ultra concentrated source of essential fish oils
Vitamin D3 Extreme™ Vitamin D3 Extreme™
50,000 IU Vitamin D3 - Prescription Strength

Natural Remedies

Secret Nutrient for Radiant Skin Secret Nutrient for Radiant Skin
Priming Your Immune System for Cold & Flu Season Priming Your Immune System for Cold & Flu Season
Breaking Through the Mental Fog Breaking Through the Mental Fog
Coenzyme Q10 - The Energy Maker Coenzyme Q10 - The Energy Maker
Everything You Always Wanted to Know About Sleep But Were Too Tired to Ask Everything You Always Wanted to Know About Sleep But Were Too Tired to Ask

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

· Become a Wholesaler
· Vendor Inquiries
· Affiliate Program
SHOP WITH CONFIDENCE
Credit Card Processing
SUBSCRIBE AND SAVE 15% NOW*
Be the first to know about new products, special discounts and the latest health news. *New subscribers only

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

© 2016 ProHealth, Inc. All rights reserved. Pain Tracker App  |  Store  |  Customer Service  |  Guarantee  |  Privacy  |  Contact Us  |  Library  |  RSS  |  Site Map