Researchers have published findings documenting biochemicalchanges in the brains of Alzheimer's victims that may prove tobe particular to the disease.
The scientists, reporting in the March 1 issue of theProceedings of the National Academy of Sciences, presentedevidence for abnormal metabolism of the lipids in nerve cellmembranes in Alzheimer's cases.
In brains from people who died with the disease, the cellmembrane ingredients choline and ethanolamine weredepleted 30 percent to 50 percent compared with normalautopsy specimens. Phospholipids were decreased by 12percent to 15 percent, while levels of phospholipid breakdownproducts were increased.
Although lipid abnormalities have been described before, thenew report by researchers from Massachusetts GeneralHospital, Massachusetts Institute of Technology, Harvard andBoston University Medical School more fully details thebiochemical changes in the brains of Alzheimer's patients.
Brains from people who died from other degenerativeneurologic diseases, or with Down's syndrome, did not show thelipid changes, suggesting that the elevation of lipid metabolitesmay be a distinctive characteristic of Alzheimer's, the scientistsconcluded.
The researchers suggested that abnormal phospholipidhandling could explain how amyloid gets deposited in thevictims' brains. Improperly exposed in defective membranes,the amyloid precursor protein could be cut by enzymes to formamyloid, the protein that so far is implicated in the nervedegeneration of the disease.
"I would have the same conclusion," agreed Boston Universityresearcher Carmela Abraham, who consults for Cephalon Corp.(NASDAQ:CEPH). The data confirmed what many researchershave thought, that a membrane abnormality is present in thedisease. "We now have a clue of what is going wrong," Abrahamsaid.
Interneuron Pharmaceuticals Inc. (NASDAQ:IPIC) is alreadystudying the therapeutic potential of two drugs available inEurope that appear to work on the membrane lipids.
Richard Wurtman, an MIT researcher and Interneuron founderwho was on the team reporting the new lipid findings, said thatone of the drugs, CDP-choline, may enhance formation of cellmembranes.
Interneuron has licensed CDP-choline from Ferrer of Spain. Thecompany has licensed another potential therapeutic, anaminopyridine that seems to increase choline levels, fromMedea Research of Italy, said Charles Casamento, president andCEO
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.