Diabetes and cholesterol dyshomeostasis involve abnormal α-synuclein and amyloid beta transport in neurodegenerative diseases

The understanding of molecular mechanisms underlying diet and Alzheimer’s disease and the cholesterol connection are important for prevention and treatment of Alzheimer’s disease linked to Type 3 diabetes and aberrant lipid metabolism. Cholesterol modulates amyloid beta generation with the ATP-binding cassette transporter 1 as a major regulator of cholesterol and phospholipids from cell membranes involved in amyloid beta transport from the brain to the liver for metabolism. In Parkinson’s disease the α-synuclein protein binds to cholesterol (tilted peptide 67-78/isooctyl chain) in cell membranes. Fatty acids, cholesterol and phospholipids such as phosphatidylinositol in membranes are sensitive to amyloid beta and α-synuclein binding/aggregation indicate the involvement of lipids in the progression of AD and PD. The global obesity and Type 2 diabetes epidemic indicate that down regulation of Sirtuin 1 is associated with increased plasma α-synuclein levels in the modulation of membrane ion channels, impairments in protein degradation with abnormal endoplasmic reticulum-mitochondrial interactions associated with disturbed peripheral amyloid beta metabolism common to both Parkinson’s disease and Alzheimer’s disease