Liver

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"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- Liver -

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Observations:

Liver, Not Brain, May Be Origin of Alzheimer’s Plaques
ScienceDaily (Mar. 3, 2011) — Unexpected results from a Scripps Research Institute and ModGene, LLC study could completely alter scientists' ideas about Alzheimer's disease -- pointing to the liver instead of the brain as the source of the "amyloid" that deposits as brain plaques associated with this devastating condition. The findings could offer a relatively simple approach for Alzheimer's prevention and treatment... 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...
http://www.sciencedaily.com/releases/2011/03/110303134435.htm

J. Gregor Sutcliffe, Peter B. Hedlund, Elizabeth A. Thomas, Floyd E. Bloom, Brian S. Hilbush. Peripheral reduction of β-amyloid is sufficient to reduce brain β-amyloid: Implications for Alzheimer's disease. Journal of Neuroscience Research, March 3, 2011 DOI: 10.1002/jnr.2260

Peripheral reduction of β-amyloid is sufficient to reduce brain β-amyloid: implications for Alzheimer's disease.
Sutcliffe JG, Hedlund PB, Thomas EA, Bloom FE, Hilbush BS.
J Neurosci Res. 2011 Jun;89(6):808-14. doi: 10.1002/jnr.22603. Epub 2011 Mar 3.
Source: Department of Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. gregorsutcliffe@aol.com
Abstract
Three loci that modify β-amyloid (Aβ) accumulation and deposition in the brains of a mouse model of Alzheimer's disease have been previously described. One encompasses the Psen2 gene encoding presenilin 2, a component of the γ-secretase activity responsible for generating Aβ by proteolysis. We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Aβ deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Aβ in both the blood and the brain, confirming brain Aβ's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease. The genes Cib1 and Zfhx1b reside within the other modifier loci and also exhibit heritable expression in the liver, suggesting that they too contribute to Aβ accumulation.

Comment in
From the liver to the blood-brain barrier: an interconnected system regulating brain amyloid-β levels. [J Neurosci Res. 2011]
PMID: 21374699 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21374699

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