Ectopic Cell Cycle Proteins Predict the Sites of Neuronal Cell Death in Alzheimer’s Disease Brain
Open accessAbstract
Alzheimer’s disease (AD) is a major dementing illness characterized by regional concentrations of senile plaques, neurofibrillary tangles, and extensive neuronal cell death. Although cell and synaptic loss is most directly linked to the severity of symptoms, the mechanisms leading to the neuronal death remain unclear. Based on evidence linking neuronal death during development to unexpected reappearance of cell cycle events, we investigated the brains of 12 neuropathologically verified cases of Alzheimer’s disease and eight age-matched, disease-free controls for the presence of cell cycle proteins. Aberrant expression of cyclin D, cdk4, proliferating cell nuclear antigen, and cyclin B1 were identified in the hippocampus, subiculum, locus coeruleus, and dorsal raphe nuclei, but not inferotemporal cortex or cerebellum of AD cases. With only one exception, control subjects showed no significant expression of cell cycle markers in any of the six regions. We propose that disregulation of various components of the cell cycle is a significant contributor to regionally specific neuronal death in AD.
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Polarities of effects are linked to differences in metabolic rates.
“One plausible idea is that polarities of effects are linked to differences in metabolic rates49-51.”
From Magnetic resonance microscopy maps widespread effects of Alzheimer’s disease on brain structures and behavior in mice (2026) · cites this paper as [51]
The Discussion compares how quickly neurons die during development and in Alzheimer’s disease, but does not link that difference to metabolic rates. Searches for metabolic rates and related terms found no passage addressing the proposed explanation for polarities of effects. The indexed passages provide no page numbers. (LLM, conf=0.73)
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- Authors
- Busser, J., Geldmacher, D. S., & Herrup, K.
- Affiliations
- Case Western Reserve University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-04-15
- Volume
- 18
- Issue
- 8
- Pages
- 2801-2807
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6792587
- OpenAlex
- W2130118447
- Cited by
- 543
- References
- 4
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 21 · 2020: 8 · 2019: 10 · 2018: 6 · 2017: 19 · 2016: 15 · 2015: 17 · 2014: 19 · 2013: 21 · 2012: 34
- FWCI
- 15.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health (AG08012)
- National Institute on Aging (AG-08012, P50AG008012)
- National Institute of Neurological Disorders and Stroke (R01NS020591, NS20591)
- 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
- Alzheimer's disease, neuronal cell death, cyclin D, CDK4, proliferating cell nuclear antigen, cyclin B1, hippocampus, subiculum, locus coeruleus, dorsal raphe nucleus, amyloid plaques, neurofibrillary tangles
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain Stem, Female, Hippocampus, Humans, Male, Middle Aged, Neurons, Proto-Oncogene Proteins, Biomarkers, Cyclins, Cell Death, Cell Cycle Proteins, Proliferating Cell Nuclear Antigen, Cyclin-Dependent Kinases, Cyclin B, Cyclin-Dependent Kinase 4, Cyclin D, Cyclin B1
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