P1-104: The binding of beta-amyloid 42 to lipid rafts containing detergent-resistant membranes of RBC ghost is enhanced by dietary docosahexaenoic acid in rats: An implication of erythrocyte functions to Alzheimer's disease

The interactions of RBC and amyloid beta peptide (Ab) are implicated in Alzheimer's disease (AD), however, the mechanisms are far from clarity. In AD, circulating Abs increase in the plasma, interact with RBCs, and affect their functions/morphology. We investigated whether Ab 1–42 interacts with caveolin1-containing lipid-rafts of detergent resistance membranes (DRMs) and whether such interactions could be modulated by oral administration of docosahexaenoic acid (DHA, C22:6, n3), an essential brain fatty acid, whose plasma levels is lower in AD patients. RBC hemolysis, RBC ghost and DRMs were prepared. DRMS-bound A b 1–42, caveolin1, and cathepsin were measured by immunomicrofluorescence assay or ELISA. A b 1–42 -induced hemolysis was reduced in the RBCs of DHA-preadministered rats. When fluorescent-labeled A b 1–42 (TAMRA-A b 1–42) was incubated with DRMs, TAMRA-A b 1–42 occupancy significantly increased in the DRMs of the DHA-preadministered rats. The levels of caveolin-1, DHA, cathepsin and membrane fluidity were high er, while cholesterol levels were truncated in the DRMs of DHA-preadministered rats, when compared with those of control rats. Additionally, when TAMRA-A b 1–42 was infused directly into the carotid veins of the rats, the TAMRA- A b 1–42 was found to a greater level in the DRMs of the DHA- preadministered rats, thus indicating that circulating A b s interact with the caveolin-1 containing lipid-rafts/caveola of the DRMs. The plasma levels of TAMRA-A b 1–42 were reduced, while that of the TAMRA-A b 1–42 in hepatic-DRMs and -cytosolic protease such as cathepsin activity also significantly increased in the post-infused DHA-preadministered rats. This demonstrates, at least partially, the contribution of hepatic DRMs-bound proteins in clearance of plasma A b 1–42 levels of DHA rats. The resistance to A b 1–42 -induced hemolysis was associated with decreases in levels of lipid peroxide, reactive oxygen species and increases in GSH levels in the RBC of DHA rats. [i] The detection of A b s, at least in part, on the surface of the RBCs of AD patients might constitute the basis of biomarkers of AD, and [ii] the enrichment of RBCs with DHA helps in plasma clearance of the amyloids, probably, by increased lipid-rafts-dependent degradative pathways and also by membrane-bound increased protease like catehpsin acivity.