The role of intracellular cholesterol on the processing of the beta-amyloid precursor protein.
The objectives of this article are to summarise evidence that amyloidogenesis is a causal factor in Alzheimer's disease, to outline the main pathways of amyloidogenesis in Alzheimer's disease, describe contemporary evidence showing that the processing of the amyloid precursor protein and amyloidogenesis is strongly influenced by the levels of intracellular cholesterol. Moreover, we shall suggest a mechanistic hypothesis that could explain the observed epidemiological links between the use of inhibitors of cholesterol biosynthesis in patients and the observed reduced risk of Alzheimer's disease.
Austen
B M
BM
Neurodegeneration Unit, Dept of Surgery, St George's Hospital Medical School, Cranmer Terrace, LONDON SW17 ORE. sghk200@sghms.ac.uk
Sidera
C
C
Liu
C
C
Frears
E
E
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000235:genetics* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008148:Lovastatin / Q000008:administration & dosage
D016564:Amyloid beta-Protein Precursor; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D008148:Lovastatin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human