Bridging integrator 1 (BIN1): form, function, and Alzheimer's disease

• BIN1 is the second most important risk locus for LOAD, after APOE.
• BIN1 affects AD risk primarily by modulating tau pathology.
• BIN1 is also involved in endocytosis, inflammation, calcium homeostasis, and apoptosis.
• BIN1 might present novel opportunities for AD therapy.

The bridging integrator 1 (BIN1) gene, also known as amphiphysin 2, has recently been identified as the most important risk locus for late onset Alzheimer's disease (LOAD), after apolipoprotein E (APOE). Here, we summarize the known functions of BIN1 and discuss the polymorphisms associated with LOAD, as well as their possible physiological effects. Emerging data suggest that BIN1 affects AD risk primarily by modulating tau pathology, but other affected cellular functions are discussed, including endocytosis/trafficking, inflammation, calcium homeostasis, and apoptosis. Epigenetic modifications are important for AD pathogenesis, and we review data that suggests the possible DNA methylation of the BIN1 promoter. Finally, given the potential contributions of BIN1 to AD pathogenesis, targeting BIN1 might present novel opportunities for AD therapy.