Amyloid β-peptide_1-40 increases neuronal membrane fluidity: Role of cholesterol and brain region

There is increasing evidence of an interaction between cholesterol dynamics and Alzheimer's disease (AD), and amyloid β-peptide may play an important role in this interaction. Aβ destabilizes brain membranes and this action of Aβ may be dependent on the amount of membrane cholesterol. We tested this hypothesis by examining effects of Aβ_1-40 on the annular fluidity (i.e., lipid environment adjacent to proteins) and bulk fluidity of rat synaptic plasma membranes (SPM) of the cerebral cortex, cerebellum, and hippocampus using the fluorescent probe pyrene and energy transfer. Amounts of cholesterol and phospholipid of SPM from each brain region were determined. SPM of the cerebellum were significantly more fluid as compared with SPM of the cerebral cortex and hippocampus. Aβ significantly increased (P ≤ 0.01) annular and bulk fluidity in SPM of cerebral cortex and hippocampus. In contrast, Aβ had no effect on annular fluidity and bulk fluidity of SPM of cerebellum. The amounts of cholesterol in SPM of cerebral cortex and hippocampus were significantly higher (P ≤ 0.05) than amount of cholesterol in SPM of cerebellum. There was significantly less (P ≤ 0.05) total phospholipid in cerebellar SPM as compared with SPM of cerebral cortex. Neuronal membranes enriched in cholesterol may promote accumulation of Aβ by hydrophobic interaction, and such an interpretation is consistent with recent studies showing that soluble Aβ can act as a seed for fibrillogenesis in the presence of cholesterol.