CLEVELAND -- No cure exists for Alzheimer's Disease (AD), but a group of researchers at Case Western Reserve University has found in test tube studies that nicotine inhibits the formation of amyloid plaque -- the toxic substance found in the brains of Alzheimer's patients and suspected as the cause of the devastating dementia of memory loss.
The research work was conducted in the laboratory of Michael Zagorski, assistant professor in the Department of Chemistry. The team reported findings in the October 22 issue of "Biochemistry," a journal of the American Chemical Society.
The amyloid plaques are abundant in AD brains, and the major component of the plaques is the beta-peptide. The beta-peptide is normally found in everyone's blood plasma and other fluids.
However, under certain environmental changes, the beta-peptides undergo a transformation from a soluble form (alpha-helix) to one that is toxic to nerve cells (beta-sheet). Both are elementary structures found in strings of amino acids that make up proteins and peptides.
A major goal of research is to find ways to prevent the toxic beta-sheets from forming.
Although cigarette smoking is hazardous to human health, previous studies in the 1990s demonstrated an inverse relationship between smoking and AD.
These findings came shortly after Zagorski published a paper in "Science" in 1992 with Colin Barrow from New Zealand on the effects of how acidity levels below pH 7 caused the toxic changes in beta-peptide structure, accelerating the transformation of the beta-peptide into amyloid plaque-like material.
Zagorski speculated that an analogous lowering of the blood pH, which may happen from over-exertion and a decrease of oxygen to the brain, may be partly responsible for amyloid plaque formation in AD brains. However, this proposition remains to be tested, he said.
Sensing a possible link in the area of his research to the potential of nicotine for interrupting the helix to beta-sheet formation, Zagorski began new research studies with nicotine.
Working under Zagorski's supervision, Arthur Salomon (who at the time was an undergraduate student and now is a graduate student at Stanford University) performed the experiments that showed nicotine inhibits production of the toxic beta-sheet structures and the accompanying formation of amyloid plaques.
Cotinine, a substance formed through metabolism of nicotine in humans, also slowed down the transformation, but it was less effective than nicotine.
Graduate students also participating in the research included Shu-chuan Jao, Keith Marcinowski, and Haiyan Shao. Robert Friedland from the Department of Neurology in CWRU's School of Medicine also contributed to the study.
The researchers are currently obtaining a three-dimensional molecular model of nicotine when it is bound to pre-transformation structure of the beta-peptide.
"This model may later facilitate the development of nicotine-like compounds that could prevent or slow down amyloid formation in AD patients," said Zagorski.
He also stresses that nicotine in tobacco is hazardous to human health, and that cigarette smoking should not be considered as a method to delay or prevent the onset of AD.
Direct research funding came from an Alzheimer's Association Faculty Scholars Award, the American Health Assistance Foundation, the National Institute on Aging, the Ohio and New York affiliates of American Federation for Aging Research, Suntory Institute of Bioorganic Research, Gliatech Incorporated, and the Ohio Board of Regents.
Indirect funding came through a grant from Philip Morris U.S.A. to Friedland.
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Toni Ferrante-Searle (amf2@po.cwru.edu) 216-368-4443 voice
Editor, "Campus News," Case Western Reserve University 216-368-3546 fax
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