Alpha adaptins show isoform‐specific association with neurofibrillary tangles in Alzheimer's disease

Abstract Aims The heterotetrameric assembly protein complex 2 (AP‐2) is a central hub for clathrin‐dependent endocytosis. The AP‐2 α‐adaptin subunit has two major isoforms, encoded by two separate genes: AP2A1 and AP2A2 . Endocytosis has been implicated in the pathogenesis of neurodegenerative disease, and recent studies linked α‐adaptins (gene variants, splicing defects and altered expression) with late‐onset Alzheimer's disease (LOAD) risk. Here, we used multiple antibodies to investigate α‐adaptin isoforms and their localization in human brains. Methods The specificities of 10 different α‐adaptin antibodies were evaluated using immunoblots after human AP2A1 and AP2A2 plasmid transfection in cultured cells. Additional immunoblot analyses were then performed on protein homogenates from control and LOAD subje