Bridging Integrator 1 (BIN1) Protein Expression Increases in the Alzheimer's Disease Brain and Correlates with Neurofibrillary Tangle Pathology
Open accessAbstract
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.
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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 [30]
The Results (page unavailable) report a decrease in the larger BIN1 iso1 band and an increase in the smaller iso9 band in Alzheimer’s disease brain, supporting the direction of the claimed shift. The Introduction gives a predicted mass of 95 kDa for the largest isoform, but our copy does not specify a 65–75 kDa mass for the smaller isoforms or establish what the other two studies reported. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrevious studies using the same antibodies employed in this analysis identified similar immunolabeling in the human brain as reported here, but attributed the labeling to neuronal soma or nucleus without comparing BIN1 immunolabeling with markers for neurons or oligodendrocytes.
“Previous studies using the same antibodies employed in our analysis identified similar immunolabeling in the human brain as reported here, but attributed the labeling to neuronal soma or nucleus without comparing BIN1 immunolabeling with markers for neurons or oligodendrocytes [13, 26, 30].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [30]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIt is generally assumed, and in a few papers described, that BIN1 is expressed in neurons.
“The findings detailed above were surprising because it is generally assumed, and in a few papers described, that BIN1 is expressed in neurons [4, 26, 30].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [30]
An increase in BIN1 levels was reported in another study of AD.
“an increase in BIN1 levels was reported in another study [30].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [30]
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Cites
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“We and others have shown that BIN1 expression is elevated in AD brains [3] and that BIN1 levels are correlated with the presence of neurofibrillary tangles [26].”
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- Authors
- Holler, C. J., Davis, P. R., Beckett, T. L., Platt, T. L., Webb, R. L., Head, E., & Murphy, M. P.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Murphy, M. Paul
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2014-10-10
- Volume
- 42
- Issue
- 4
- Pages
- 1221-1227
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC4198456
- OpenAlex
- W1680905070
- Cited by
- 145
- References
- 2
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 12 · 2023: 6 · 2022: 28 · 2021: 14 · 2020: 16 · 2019: 6 · 2018: 13 · 2017: 11 · 2016: 8 · 2015: 8
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (TL1TR000115, UL1TR000117)
- National Institute on Aging (AG-028383, P50 AG 16573, P30AG028383, P01AG005119, P50AG016573, AG-005119, P50AG025688)
- National Institute of General Medical Sciences (GM103486, P20GM103486)
- National Institute of Neurological Disorders and Stroke (T32NS007480, NS083692, R01NS058382, NS-058382, R21NS083692)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01-HD-90011)
- 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
- MeSH terms
- Aged, 80 and over, Alzheimer Disease, Brain, Electrophoresis, Polyacrylamide Gel, Female, Humans, Immunohistochemistry, Isomerism, Male, Nuclear Proteins, Blotting, Western, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Tumor Suppressor Proteins, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Plaque, Amyloid
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