Role of Phosphatidylinositol Clathrin Assembly Lymphoid-Myeloid Leukemia (PICALM) in Intracellular Amyloid Precursor Protein (APP) Processing and Amyloid

Understanding cellular mechanisms involved in APP processing may reveal novel targets for intervention.OneofthepathologicalhallmarksofAlzheimerdiseaseistheaccumulation of amyloid plaques in the extracellular space inthe brain. Amyloid plaques are primarily composed of aggre-gated amyloid peptide (A ), a proteolytic fragment of thetransmembrane amyloid precursor protein (APP). For APP tobe proteolytically cleaved into A , it must be internalized intothe cell and trafficked to endosomes where specific proteasecomplexes can cleave APP. Several recent genome-wide associ-ation studies have reported that several single nucleotidepolymorphisms (SNPs) in the phosphatidylinositol clathrinassemblylymphoid-myeloidleukemia(