Cholesterol and neuronal susceptibility to beta-amyloid toxicity

Alzheimer's disease (AD) is a devastating neurocognitive disorder rapidly growing across the elderly population. Although few cases arise due to genetic mutations, sporadic AD is the most common form of this disease. Therefore, there is a continuing research effort to discover a unifying cause of this form of AD. To date, the only strong genetic correlate to the sporadic AD is inheritance of the apolipoprotein E4 (ApoE4) allele, whose encoded protein is involved in cholesterol transport in the central nervous system. This genetic link has prompted a series of studies on the potential molecular mechanisms by which cholesterol could modulate neuronal degeneration in the context of AD. In this review, we discussed the involvement of cholesterol in the production of the pathological hallmarks of the disease and how it might alter the susceptibility of cells to AD-related insult. Finally, we discussed the use of cholesterol-lowering drugs as a potential preventative approach in AD.