BIN1 Is Decreased in Sporadic but Not Familial Alzheimer’s Disease or in Aging
Open accessAbstract
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 (r(s)=-0.084, p=0.698), insoluble Aβ (r(s)=0.237, p=0.269), Aβ plaque load (r(s)=0.063, p=0.771) or phospho-tau load (r(s)=-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.
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All three studies report a decrease of the ~90 kDa BIN1:H isoform and an increase of the ~65-75 kDa BIN1:L isoforms.
“Uniformly, all three studies report a decrease of the ~90 kDa BIN1:H isoform and an increase of the ~65-75 kDa BIN1:L isoforms (Fig. 3).”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [29]
The Results section (page not available) reports that BIN1 appears as multiple isoform bands and that total BIN1 protein decreases in sporadic Alzheimer’s disease; the Figure 1 caption specifies that densitometry included all bands. It does not report a decrease specifically in the ~90 kDa isoform or an increase in the ~65–75 kDa isoforms, so it does not support the claimed uniform pattern across three studies. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA significant decrease in BIN1 levels was observed by immunoblot analysis in one study of AD.
“a significant decrease in BIN1 levels was observed by immunoblot analysis in one study [29]”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [29]
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“The brain areas analysed did differ between the sporadic and familial AD cohorts, but both the frontal cortex and the hippocampus are areas known to be associated with AD [27-29].”
BackgroundVariation and genetic control of protein abundance in humans
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“Whereas, a significant decrease in BIN1 levels was observed by immunoblot analysis in one study [29], an increase in BIN1 levels was reported in another study [30].”
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- Authors
- Glennon, E. B. C., Whitehouse, I. J., Miners, J. S., Kehoe, P. G., Love, S., Kellett, K. A. B., & Hooper, N. M.
- Affiliations
- University of Leeds (GB)
- University of Bristol (GB)
- Corresponding author
- Kellett, Katherine A. B.
- Hooper, Nigel M.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-10-21
- Volume
- 8
- Issue
- 10
- Pages
- e78806
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3804620
- OpenAlex
- W1968344841
- Cited by
- 81
- References
- 7
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 16 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 1 · 2014: 4
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Explore Bristol Research (submittedVersion)
- Funders
- Medical Research Council (G0802189)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- BIN1, sporadic Alzheimer's disease, familial Alzheimer's disease, amyloid-beta, amyloid plaques, tau phosphorylation, endocytosis, APP processing, brain aging, frontal cortex, hippocampus, siRNA knockdown, SH-SY5Y cells
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Nuclear Proteins, Tumor Suppressor Proteins, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Gene Knockdown Techniques
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