Cholesterol paradox: is high total or low HDL cholesterol level a risk for Alzheimer's disease?

Cholesterol is an essential component of membranes for maintaining their structure and functions. The discovery that possession of apolipoprotein E (apoE), allele epsilon4 is a strong risk factor for Alzheimer's disease (AD) leads us to focus on the role of cholesterol in the pathogenesis of AD. Accumulating epidemiological and biological evidence suggests the link between the serum cholesterol level and the development of AD, and the potential therapeutic effectiveness of statins for AD and mild cognitive impairment (MCI), whereas other lines of evidence show controversial results. Cholesterol is known to interact with amyloid beta-protein (Abeta) in a reciprocal manner: cellular cholesterol levels modulate Abeta generation, whereas Abeta alters cholesterol dynamics in neurons, leading to tauopathy. In this review, the relationship between the cholesterol levels in serum or cerebrospinal fluid (CSF) and the induction of AD is discussed. The mechanism(s), if this is the case, of how cholesterol in the central nervous system (CNS) is involved in the induction of pathologies of AD including Abeta generation and tauopathy, and how statins prevent it are also discussed.