BRCA1 May Play Role in Neurodegeneration

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BRCA1 May Play Role in Neurodegeneration
BRCA1 May Play Role in Neurodegeneration

Recent findings indicate that that the BRCA1 gene associated with breast and ovarian cancer may also play a role in Alzheimer's disease.

The study results, published in Nature Communications, suggest that low levels of BRCA1 protein in the brain may contribute to dementia by disrupting DNA repair.

The researchers, led by Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and professor of neurology at the University of California, San Francisco, found reduced levels of BRCA1 in the brains of Alzheimer's patients, as well as in mouse models of Alzheimer's. When the researchers knocked down neuronal BRCA1 in the dentate gyrus of wild-type mice, they observed an increase in DNA double-strand breaks, neuronal shrinkage, and impairments in synaptic plasticity, learning, and memory. The effects were exacerbated in mice with low levels of human amyloid precursor protein and beta-amyloid overexpression.

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In primary neuronal cultures, beta-amyloid oligomers reduced BRCA1 levels by 50% and increased levels of DNA double-strand breaks by 70%.

“An emerging theme in neurodegeneration research is that normal DNA repair protects against damage that causes neurons to die in dementia and related disorders. This study supports and strengthens that theme by showing that beta-amyloid decreases the levels of the DNA repair gene BRCA1, and at the same time inhibits the ability to form new memories,” said Roderick Corriveau, PhD, of the NIH's National Institute of Neurological Disorders and Stroke.

Further research is necessary to determine whether BRCA1 is a potential target for treatment of dementia. The researchers also want to explore whether mutations in BRCA1, which lead to cancer, also affect brain function.

References

  1. Suberbielle E, Djukic B, Evans M, et al. DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice. Nat Commun. 2015;6:8897.
  2. NIH press release
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