The aluminium-amyloid cascade hypothesis and Alzheimer's disease.

Abstract

Aluminium (Al) is found associated with beta-amyloid (Abeta) in the brain in Alzheimer's disease. Al precipitates Abeta in vitro as distinct fibrillar structures composed of beta-pleated sheets of peptide. The aetiology of their association in vivo is not known. Al is known to increase the brain Abeta burden in experimental animals and this might be due to a direct influence upon Abeta anabolism or direct or indirect affects upon Abeta catabolism. It is difficult to rationalise from an evolutionary perspective the precipitation and persistence of Abeta in vivo. However, Al has not been subject to the same evolutionary pressures as Abeta, it is a recent addition to the biotic environment, and its precipitation of Abeta may have only been subjected to natural selection in the recent past. Whether AD is also part of this ongoing selection process remains to be elucidated