The link between cholesterol and Alzheimer's disease

A leading hypothesis on the pathophysiology of Alzheimer's disease (AD) is the mis-metabolism of amyloid precursor protein. This mis-metabolism causes the 42-amino acid form of A beta(A beta 42) to form oligomers that in turn start a chain of events leading to the accumulation of amyloid plaques. Vascular factors such as hypertension, hypercholesterolemia and diabetes as well as the inheritance of the 0 allele of the ApoE gene are risk factors for AD. These risks are thought to promote the production of beta-amyloid (A beta). An association between cholesterol and the development of AD was suggested in 1994 and since then, research has confirmed a link between cholesterol and the development of AD. A high cholesterol level in mid-life is a risk for AD and statins i.e. cholesterol-lowering drugs, reduce this risk. Statins inhibit enzymes involved in the endogenous synthesis of cholesterol and evidence is mounting that they also affect enzymes in A beta metabolism i.e. beta-secretase. This normalises the breakdown of the precursor of A beta, amyloid precursor protein, thereby promoting the non-amyloidogenic pathway. This review focusses on the link between cholesterol and Alzheimer's disease.