New evidence for an active role of aluminum in Alzheimer's disease.
Application of molecular biological techniques and sensitive elemental analysis have produced new evidence implicating aluminum as an important factor in down regulation of neuronal protein metabolism. Aluminum in Alzheimer's disease may act by electrostatically crosslinking proteins, particularly the methionine containing histone H1(0), and DNA. The consequence of such crosslinking is reduced transcription of at least one neuron specific gene, the low molecular weight component of neurofilaments. In the superior temporal gyrus in Alzheimer's disease, down regulation of this gene occurs in approximately 86% of surviving neurons and, therefore, aluminum must be considered as having an active role in the pathogenesis. Epidemiological studies are reviewed that independently support the hypothesis that environmental aluminum is a significant risk factor. Preliminary evidence also suggests that a disorder in phosphorylation may be an important initiating factor.
McLachlan
D R
DR
Department of Physiology, University of Toronto, Ontario, Canada.
Lukiw
W J
WJ
Kruck
T P
TP
D000535:Aluminum / Q000378:metabolism* / Q000633:toxicity; D000544:Alzheimer Disease / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002843:Chromatin / Q000187:drug effects; D003432:Cross-Linking Reagents; D005786:Gene Expression Regulation / Q000187:drug effects*; D006657:Histones / Q000378:metabolism*; D006801:Humans
D002843:Chromatin; D003432:Cross-Linking Reagents; D006657:Histones; D000535:Aluminum