Apolipoproteins and β Amyloid Transport Pathway

Abstract

Cholesterol metabolism has been viewed as an important step in the development of Alzheimer's disease, since it was shown that the ~4 allele of apolipoprotein E (APO€) gene is a genetic risk and modifies age-at-onset of Alzheimer's disease. Although the knowledge of the effect of cholesterol in the neuronal cell has been recently accumulated, the link between systemic and brain cholesterol metabolism remains to be elucidated. Lipoproteins in cerebrospinal fluid (CSF) are fractionated only to high-density lipoprotein (HDL), and contain apolipoprotein (apo) A-I, E, A-11, and J. Whereas apoE is produced in the brain, apoA-I and apoA-II in cerebrospinal fluid, the major components of plasma HDL cholesterol, originate from plasma. Plasma HDL is thought to act in reverse cholesterol transport, and in vitro experiments indicated that these apolipoproteins and albumin show a high affinity binding to p amyloid. In patients with Alzheimer's disease, plasma apoA-I and apoA-I1 levels are significantly decreased, which is possibly related to the deposition of p amyloid in the brain, and to the p amyloid transport pathway.