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Cholesterol hastens Alzheimer's

Aß aggregates (white) form faster in the presence (right) of cholesterol aldehydes. Kelly/NAS

Results from Qinghai Zhang, Jeffery Kelly (Scripps Research Institute, La Jolla, CA), and colleagues suggest that evil metabolites may accelerate Alzheimer's disease (AD) by promoting protein misfolding. This folding effect may explain why inflammation and high cholesterol are risk factors for AD.

AD results from aggregates of a misfolded form of amyloid ß peptide (Aß). Misfolding occasionally results from processing flaws or mutations in the Aß precursor, but most patients have normal Aß. Zhang et al. show that even normal Aß folds abnormally when cholesterol by-products modify it.

Cholesterol itself did not affect Aß, but cholesterol modified by reactive oxygen species (which are produced during inflammation) to generate an aldehyde group reacted with Aß and made it more hydrophobic. This altered form aggregates at much lower concentrations than does normal Aß–concentrations that are found in the brain.

Although brain samples did not show higher levels of the cholesterol aldehydes in AD patients, only small amounts of these metabolites are needed to jump start aggregation. "The creation of compounds that are reactive could be from an event occurring years before an individual presents with AD," says Kelly. So, as boxers already know, one good knock on the head might do more lasting damage than just a fleeting headache.

Reference:

Zhang, Q., et al. 2004. Proc. Natl. Acad. Sci. USA. 10.1073/pnas.0400924101.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 1042K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?