Mar 112011
 

Readers,

Two recent papers* have shed light on the role of the liver in modulating beta-amyloid levels in the brain, and potentially the course of Alzheimer’s disease.

First, researchers at the University of California, Irvine discovered that markedly depleted amounts of an omega-3 fatty acid in brain tissue samples from Alzheimer’s patients may be due to the liver’s inability to produce the complex fat. Low levels of docosahexaenoic acid, or DHA, have been associated with Alzheimer’s, but no cause had been identified. In postmortem liver tissue from Alzheimer’s patients, the UCI team found a defect in the organ’s ability to make DHA from shorter molecules present in leafy plants and other foods. Previous studies have shown that most brain DHA is manufactured in the liver. Additionally, they found that the greater the amount of Alzheimer’s-related cognitive problems experienced in life by the patients, the lower were their liver DHA levels.

Secondly, researchers from the Scripps Institute in La Jolla, compared two strains of mice that were genetically engineered to develop Alzheimer’s disease. Earlier work had found that one strain was protected against the buildup of beta amyloid in the brain, compared with the other. The research team identified three genes that could confer such protection. They showed that cells in the liver of the protected mice did not express, or turn on, these genes, as much as liver cells of the other mice. Further, they found this lower level of expression protected against accumulation of beta amyloid in the brain. One of these genes, called Presenilin 2, is involved in the production of beta amyloid, and has been linked to early onset Alzheimer’s disease in humans. But previous work had focused on expression of this gene in the brain, not other tissues that produce beta amyloid.

The researchers wanted to give the mice a drug that would reduce levels of beta amyloid in only the blood. They chose the drug Gleevec (which is used to treat leukemia) because it cannot cross the blood-brain barrier. Gleevec had previously been shown to reduce the amount of beta amyloid in the brain when pumped into the brain, but researchers had not yet looked for this effect after injecting it into the bloodstream. They found that administering Gleevec for a week reduced the amount of beta amyloid in the brain by 50 percent, even though the drug cannot get into the brain. Thereby, raising the possibility that by lowering beta-amyloid in the liver, we may be able to lower it in the brain as well.

* Giuseppe Astarita, Kwang-Mook Jung, Nicole C. Berchtold, Vinh Q. Nguyen, Daniel L. Gillen, Elizabeth Head, Carl W. Cotman, Daniele Piomelli, Silvana Gaetani. Deficient Liver Biosynthesis of Docosahexaenoic Acid Correlates with Cognitive Impairment in Alzheimer’s Disease. PLoS ONE, 2010; 5 (9): e12538.

* J. Gregor Sutcliffe, Peter B. Hedlund, Elizabeth A. Thomas, Floyd E. Bloom, Brian S. Hilbush. Peripheral reduction of ß-amyloid is sufficient to reduce brain ß-amyloid: Implications for Alzheimer’s disease . Journal of Neuroscience Research: 3 MAR 2011 DOI: 10.1002/jnr.22603.

Michael S. Rafii, M.D., Ph.D.
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

  One Response to “The Liver and Alzheimer’s”

  1. Question: When the liver is producing beta amyloid, is it because the liver is not healthy, or because of a genetic defect ? What conditions cause the production of beta amyloid, from the liver ? ie. Would holistic care of the liver, help decrease beta amyloid production, by the liver ?

 Leave a Reply

(required)

(required)

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>

Alz.org main site  |  Research  |  Advocacy  |  Care and support  |  Message boards  |  Disclaimer  |  Donate  |  Contact us  |  Sign up for e-news
© 2011 Alzheimer's Association | Blog Suffusion theme by Sayontan Sinha