The Effects of Glycerophospholipids and Fatty Acids on APP Processing: Implications for Alzheimer’s Disease

Abstract Alzheimer’s disease (AD) is pathologically characterized by the massive accumulation of amyloid-β (Aβ) peptides, a small cleavage product of the amyloid precursor protein(APP). The release of Aβ peptides out of the large type I transmembrane proteinAPP involves several membrane-spanning secretases. This review summarizes the influence of lipids and membrane properties on APP processing as well as lipid alterations found in the brain of AD affected individuals. Main focus is addressed to glycerophospholipids, the primary component of cellular membranes. The influence of the phospholipid polar head group and the physical properties of the fatty acid (FA) carbon chain, for example, polyunsaturated FAs and trans fatty acids, on APP processing and AD is reviewed in detail. Furthermore, as there is growing evidence for possible dietary risk factors in the development of AD, an overview of the main epidemiological studies analyzing the impact of dietary FAs on AD is given.