Increased Expression of TrkB and Capzb2 Accompanies Preserved Cognitive Status in Early Alzheimer Disease Pathology
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) may influence brain reserve, the ability of the brain to tolerate pathological changes without significant decline in function. Here, we explore whether a specifically vulnerable population of human neurons shows a compensatory response to the neuropathological changes of Alzheimer disease (AD) and whether that response depends on an upregulation of the BDNF pathway. We observed increased neuronal TrkB expression associated with early-stage AD pathology (Braak and Braak stages I-II) in hippocampal CA1 region samples from cognitively intact Framingham Heart Study subjects (n = 5) when compared with cognitively intact individuals with no neurofibrillary tangles (n = 4). Because BDNF/TrkB signaling affects memory formation and retention through modification of the actin cytoskeleton, we examined the expression of actin capping protein β2 (Capzb2), a marker of actin cytoskeleton reorganization. Capzb2 expression was also significantly increased in CA1 hippocampal neurons of cognitively intact subjects with early-stage AD pathology. Our data suggest that increased expression of TrkB and Capzb2 accompanies adequate brain reserve in the initial stages of AD pathology. In subsequent stages of AD, the higher levels of TrkB and Capzb2 expression achieved may not be sufficient to prevent cognitive decline.
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Serum BDNF parallels relative difference in BDNF levels, but BDNF levels may be substantially higher, have attenuated effects over time, and may be subject to variability because of differences in expression levels of BDNF receptors.
“Although serum BDNF parallels relative difference in BDNF levels, BDNF levels may be substantially higher, have attenuated effects over time, and may be subject to variability of effect because of differences in the expression levels of BDNF receptors [8].”
From Associations between social relationship measures, serum brain-derived neurotrophic factor, and risk of stroke and dementia (2017) · cites this paper as [8]
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- Authors
- Kao, P. F., Banigan, M. G., Vanderburg, C. R., McKee, A. C., Polgar, P. R., Seshadri, S., & Delalle, I.
- Affiliations
- Boston University (US)
- Harvard University (US)
- Corresponding author
- Delalle, Ivana
- ORCID
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-07
- Volume
- 71
- Issue
- 7
- Pages
- 654-664
- ISSN
- 0022-3069 (ISSN-L)
- PMC
- PMC3398703
- OpenAlex
- W2023092508
- Cited by
- 31
- References
- 53
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2017: 8 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5t32ag000115-25)
- National Institute on Aging (R01AG031287, T32-AG-000115, 5T32AG000115-25, R01AG016495, P30AG013846, 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 › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- Alzheimer's disease, TrkB, brain-derived neurotrophic factor, brain reserve, CA1 pyramidal neurons, neurofibrillary tangles, Braak stages, actin cytoskeleton, cognitive preservation, Framingham Heart Study
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Dementia, Female, Hippocampus, Humans, Male, Neuropsychological Tests, RNA, Messenger, Signal Transduction, Up-Regulation, Silver Staining, Brain-Derived Neurotrophic Factor, Receptor, trkB, Actin Capping Proteins, Laser Capture Microdissection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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