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Cited by 45Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Subcellular Changes in Bridging Integrator 1 Protein Expression in the Cerebral Cortex During the Progression of Alzheimer Disease Pathology

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Adams, Stephanie L., Tilton, Kathy, Kozubek, James A., Seshadri, Sudha, Delalle, Ivana·2016·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nlw056PMC PMC6281026
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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.

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  • Adams and colleagues revealed weak BIN1 immunoreactivity in a subset of neurons in patients with AD.

    “their study revealed weak BIN1 immunoreactivity in a subset of neurons in patients with AD.”

    From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [58]

    The Results report BIN1 cytoplasmic immunoreactivity in a subset of CA1 pyramidal neurons in patients with AD (mean 32.21%). They describe a weaker BIN1 signal in AD neuropil, not weak immunoreactivity in those neurons; the Discussion instead reports an increase in BIN1-positive neurons. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Adams and colleagues reported BIN1 expression in white matter and oligodendrocytes in the brain but not in neurons in healthy controls.

    “Adams and colleagues reported BIN1 expression in white matter and oligodendrocytes in the brain but not in neurons in healthy controls [58], consistent with our results.”

    From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [58]

    The Results section reports BIN1 expression in white matter and oligodendrocytes in healthy controls. But it also reports cytoplasmic BIN1 signal in a mean of 3.34% of CA1 pyramidal neurons in those controls, so the claim that BIN1 was not expressed in neurons is too absolute. Our copy provides no page number for these passages. (LLM, conf=0.94)

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Authors
Adams, S. L., Tilton, K., Kozubek, J. A., Seshadri, S., & Delalle, I.
Affiliations
Broad Institute (US)
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2016-06-26
Volume
75
Issue
8
Pages
779-790
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nlw056
PMC
PMC6281026
OpenAlex
W2468488057
Cited by
45
References
9
Citations by year
2026: 4 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 13 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 3 · 2016: 1
FWCI
3.49
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institute on Aging (P30AG010129, R01AG033193, R01AG008122)
  • National Institute of Neurological Disorders and Stroke (R01NS017950)
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, Alzheimer's disease, protein expression, cerebral cortex, hippocampal CA1, neuropil, neuritic plaques, neurofibrillary tangles, oligodendrocytes, pyramidal neurons, disease progression, subcellular localization, amygdala, prefrontal cortex, temporal cortex, occipital cortex
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, Female, Humans, Male, Middle Aged, Nuclear Proteins, Gene Expression, Disease Progression, Tumor Suppressor Proteins, Intracellular Space, Adaptor Proteins, Signal Transducing

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