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Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress
Published on: May 7, 2014
BRCA1 may modulate neuronal cell cycle re-entry in Alzheimer disease
Teresa A Evans1, Arun K Raina, André Delacourte
1Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
International Journal of Medical Sciences
|May 17, 2007
Summary
Alzheimer disease neurons re-enter the cell cycle, a process linked to BRCA1 presence in neurofibrillary tangles. This contrasts with normal aging, suggesting different tangle origins and a role for cell cycle regulators in Alzheimer disease pathogenesis.
Area of Science:
- Neuroscience
- Cell Biology
- Oncology
Background:
- Alzheimer disease (AD) is characterized by neuronal degeneration and neurofibrillary tangles (NFTs) that correlate with cognitive decline.
- NFTs in AD exhibit cell cycle markers, indicating neuronal cell cycle re-entry, but the underlying mechanisms remain unclear.
- Dysregulated cell cycle control is a hallmark of cancer, prompting investigation into oncogenic proteins in neurodegeneration.
Purpose of the Study:
- To investigate the role of BRCA1, a cell cycle regulator, in Alzheimer disease pathogenesis.
- To determine the localization of BRCA1 within neurofibrillary tangles in Alzheimer disease brain tissue.
- To compare BRCA1 expression in Alzheimer disease NFTs versus NFTs in normal aging.
Main Methods:
- Immunohistochemical analysis of human brain tissue from Alzheimer disease and age-matched control cases.
- Examination of BRCA1 localization in neurofibrillary tangles and other neuronal structures.
- Assessment of phosphorylated tau-positive NFTs in relation to BRCA1 presence.
Main Results:
- Intense and specific localization of BRCA1 to neurofibrillary tangles was observed in Alzheimer disease brains.
- BRCA1 was less abundant in clinically normal aged brain tissue.
- Surprisingly, BRCA1 was absent in some phosphorylated tau-positive NFTs from normal aging brains, but present in all Alzheimer disease cases.
Conclusions:
- BRCA1 is a key component of neurofibrillary tangles in Alzheimer disease, further defining the cell cycle re-entry phenotype.
- The distinct presence of BRCA1 in Alzheimer disease NFTs suggests a different genesis compared to NFTs found in normal aging.
- These findings implicate alterations in cell cycle regulatory proteins, like BRCA1, in the neurodegenerative processes of Alzheimer disease.
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