Affiliations: [a] Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA | [b] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [c] Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, USA | [d] University of Kentucky Center for Muscle Biology, University of Kentucky, Lexington, KY, USA
Correspondence:
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Correspondence to: M. Paul Murphy, MA, PhD, University of Kentucky, 800S. Limestone, 211 Sanders-Brown Center on Aging, Lexington, KY 40536-0230, USA. Tel.: +1 859 218 3811; Fax: +1 859 257 9479; E-mail: [email protected].
Abstract: Recent genome wide association studies have implicated bridging integrator 1 (BIN1) as a late-onset Alzheimer's disease (AD) susceptibility gene. There are at least 15 different known isoforms of BIN1, with many being expressed in the brain including the longest isoform (iso1), which is brain-specific and localizes to axon initial segments and nodes of Ranvier. It is currently unknown what role BIN1 plays in AD. We analyzed BIN1 protein expression from a large number (n = 71) of AD cases and controls from five different brain regions (hippocampus, inferior parietal cortex, inferior temporal cortex, frontal cortex (BA9), and superior and middle temporal gyri). We found that the amount of the largest isoform of BIN1 was significantly reduced in the AD brain compared to age-matched controls, and smaller BIN1 isoforms were significantly increased. Further, BIN1 was significantly correlated with the amount of neurofibrillary tangle (NFT) pathology but not with either diffuse or neuritic plaques, or with the amount of amyloid-β peptide. BIN1 is known to be abnormally expressed in another human disease, myotonic dystrophy, which also features prominent NFT pathology. These data suggest that BIN1 is likely involved in AD as a modulator of NFT pathology, and that this role may extend to other human diseases that feature tau pathology.
