Lipid metabolism, epidemiology, and the mechanisms of Alzheimer's disease.

Global variations in the incidence and prevalence of Alzheimer's disease (AD) have not been explained. Patterns of dietary intake of fats and other nutrients may be partly responsible. Recent work with transgenic mice overexpressing the beta-amyloid precursor protein suggests that anti-Abeta antibodies enhance clearance of the Abeta protein from the brain and reduce plaque burden. This has been shown even with anti-Abeta antibodies that do not enter the brain. Many factors other than circulating anti-Abeta antibodies may influence this important process of Abeta clearance, including the Abeta-binding elements, apolipoproteins E and J, circulating LDL, HDL, and LRP, alpha-2-macroglobulin, and transthyretin. Also important may be clearance of antibody-antigen complexes from the circulation, as well as complement, metals, and estrogen. Dietary intake of lipids may influence the ability of Abeta-binding proteins to enhance clearance of Abeta from the brain to blood. Understanding processes of Abeta clearance from brain may aid in determining the causes of AD in individuals, as well as the causes of global variations in incidence and prevalence of the disease.