Bridging integrator 1 (BIN1) protein expression increases in the alzheimer's disease brain and correlates with neurofibrillary tangle pathology

Christopher J. Holler, Paulina R. Davis, Tina L. Beckett, Thomas L. Platt, Robin L. Webb, Elizabeth Head, M. Paul Murphy

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

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.

Original languageEnglish
Pages (from-to)1221-1227
Number of pages7
JournalJournal of Alzheimer's Disease
Volume42
Issue number4
DOIs
StatePublished - 2014

Bibliographical note

Publisher Copyright:
© 2014 IOS Press and the authors. All rights reserved.

Keywords

  • Alzheimer's disease
  • ZNF9
  • amyloid-β peptide
  • cellular nucleic acid binding protein
  • myotonic dystrophy
  • tau

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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