Dementia Japan 24: 29-36, 2010

The significance of lipids in Aβ metabolism:From the point of view of cholesterol paradox in the development of Alzheimer's disease

Makoto Michikawa

Department of Alzheimer's Disease Research, National Center for Geriatrics and Gerontology (NCGG)

    The cholesterol metabolism in the brain is supposed to be independently and uniquely regulated, because brain is segregated from the systemic circulation by the blood-brain barrier.  It has been shown that cholesterol supplied as a lipoprotein complex, i.e., high-density-lipoprotein (HDL), is critical for the maturation of synapses and the maintenance of synaptic plasticity.  Apolipoprotein E (ApoE) is the major apolipoprotein generating HDL in the brain, and the discovery that possession of ApoE allele ε4 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, whereas other lines of evidence show controversial results.  In this review, the relationship between the altered cholesterol metabolism in serum or cerebrospinal fluid and the induction of AD is discussed and a new idea to get better understanding this relationship including the controversial results is suggested.

Address correspondence to Dr. Makoto Michikawa, Department of Alzheimer's Disease Research, National Center for Geriatrics andGerontology (NCGG) (36-3 Gengo, Morioka, Obu, Aichi 474-852, Japan)