Subcellular changes in bridging integrator 1 protein expression in the cerebral cortex during the progression of Alzheimer disease pathology

Stephanie L. Adams, Kathy Tilton, James A. Kozubek, Sudha Seshadri, Ivana Delalle

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Genome-wide association studies have established BIN1 (Bridging Integrator 1) as the most significant late-onset Alzheimer disease (AD) susceptibility locus after APOE. We analyzed BIN1 protein expression using automated immunohistochemistry on the hippocampal CA1 region in 19 patients with either no, mild, or moderate-To-marked AD pathology, who had been assessed by Clinical Dementia Rating and CERAD scores. We also examined the amygdala, prefrontal, temporal, and occipital regions in a subset of these patients. In non-demented controls without AD pathology, BIN1 protein was expressed in white matter, glia, particularly oligodendrocytes, and in the neuropil in which the BIN1 signal decorated axons. With increasing severity of AD, BIN1 in the CA1 region showed: 1) sustained expression in glial cells, 2) decreased areas of neuropil expression, and 3) increased cytoplasmic neuronal expression that did not correlate with neurofibrillary tangle load. In patients with AD, both the prefrontal cortex and CA1 showed a decrease in BIN1-immunoreactive (BIN1-ir) neuropil areas and increases in numbers of BIN1-ir neurons. The numbers of CA1 BIN1-ir pyramidal neurons correlated with hippocampal CERAD neuritic plaque scores; BIN1 neuropil signal was absent in neuritic plaques. Our data provide novel insight into the relationship between BIN1 protein expression and the progression of AD-Associated pathology and its diagnostic hallmarks.

Original languageEnglish (US)
Pages (from-to)779-790
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number8
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • Alzheimer disease
  • BIN1
  • Glia
  • Hippocampus
  • Neuropil
  • Pyramidal neurons
  • White matter

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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