Aβ 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 β peptide (Aβ). Misfolding occasionally results from processing flaws or mutations in the Aβ precursor, but most patients have normal Aβ. Zhang et al. show that even normal Aβ folds abnormally when cholesterol by-products modify it.

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

The Rockefeller University Press
2004
The Rockefeller University Press
2004
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