Cholesterol and Alzheimer's disease--is there a relation?
The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of beta-amyloid (Abeta42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques. Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the epsilon4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Abeta42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD. A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Abeta metabolism, i.e., alpha-secretase and beta-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway. In this review, investigations focusing on cholesterol and Alzheimer's disease are presented.
Sjögren
Magnus
M
Department of Experimental Geriatrics, Neurotec, Karolinska Institute, Huddinge, Sweden. magnus.sjogren@organon.com
Mielke
Michelle
M
Gustafson
Deborah
D
Zandi
Peter
P
Skoog
Ingmar
I
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases; D002784:Cholesterol / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human