BIN1 Is Decreased in Sporadic but Not Familial Alzheimer's Disease or in Aging

Elizabeth B. C. Glennon, Isobel J. Whitehouse, J. Scott Miners, Patrick G. Kehoe, Seth Love, Katherine A. B. Kellett*, Nigel M. Hooper

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

53 Citations (Scopus)

Abstract

Bridging integrator 1 (BIN1) has been implicated in sporadic Alzheimer's disease (AD) by a number of genome wide association studies (GWAS) in a variety of populations. Here we measured BIN1 in frontal cortex samples from 24 sporadic AD and 24 age-matched non-dementia brains and correlated the expression of this protein with markers of AD. BIN1 was reduced by 87% (p=0.007) in sporadic AD compared to non-dementia controls, but BIN1 in sporadic AD did not correlate with soluble Aβ (rs=-0.084, p=0.698), insoluble Aβ (rs=0.237, p=0.269), Aβ plaque load (rs=0.063, p=0.771) or phospho-tau load (rs=-0.160, p=0.489). In contrast to our findings in sporadic AD, BIN1 was unchanged in the hippocampus from 6 cases of familial AD compared to 6 age-matched controls (p=0.488). BIN1 declined with age in a cohort of non-dementia control cases between 25 and 88 years but the correlation was not significant (rs=-0.449, p=0.081). Although BIN1 is known to have a role in endocytosis, and the processing of the amyloid precursor protein (APP) to form amyloid-β (Aβ) peptides is dependent on endocytosis, knockdown of BIN1 by targeted siRNA or the overexpression of BIN1 in a human neuroblastoma cell line (SH-SY5Y) had no effect on APP processing. These data suggest that the alteration in BIN1 is involved in the pathogenesis of sporadic, but not familial AD and is not a consequence of AD neurodegeneration or the ageing process, a finding in keeping with the numerous GWAS that implicate BIN1 in sporadic AD. However, the mechanism of its contribution remains to be established.
Original languageEnglish
Article number78806
Pages (from-to)e78806
Number of pages11
JournalPLoS ONE
Volume8
Issue number10
DOIs
Publication statusPublished - 21 Oct 2013

Structured keywords

  • Dementia Research Group

Keywords

  • GENOME-WIDE ASSOCIATION
  • A-BETA
  • CHOLINESTERASE-INHIBITORS
  • AMPHIPHYSIN ISOFORM
  • IDENTIFIES VARIANTS
  • PRION PROTEIN
  • LIPID RAFTS
  • ENDOCYTOSIS
  • CLU
  • TRANSCRIPTOME

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