Low BRCA1 Levels Could Contribute to Alzheimer's

Defective DNA repair mechanisms may contribute to Alzheimer's disease.

Breast cancer gene 1 (BRCA1) produces tumor suppressor hormones that play a key role in repairing damaged DNA.

When the BRCA1 gene is altered (mutated), DNA damage may not be repaired properly, which may lead to cancer. In fact, mutant forms of BRCA1 are associated with breast and ovarian cancers.

The functions of BRCA1 in the brain are not fully understood, but now, new research funded by the National Institutes of Health suggests that low levels of BRCA1 in the brain may contribute to dementia.1,2

The study authors suspected that defects in DNA repair mechanisms could contribute to cognitive decline in Alzheimer's disease. They discovered low levels of BRCA1 in the brains of Alzheimer’s patients who died and mouse models of Alzheimer’s, and during an experiment in which BRCA1 levels were reduced in the brains of healthy mice, they noticed that brain cells shrank and became dysfunctional. The mice also developed cognitive problems.

The brains of patients with Alzheimer’s have amyloid plaques consisting largely of insoluble deposits of beta-amyloid. These amyloid plaques are found in the spaces between the neurons.

The research team discovered that adding beta-amyloid to neurons in a dish lowered levels of BRCA1, suggesting that DNA damage in brain cells caused by decreasing levels of BRCA1 may contribute to dementia.

Further studies are necessary to determine whether a drug that restores BRCA1 levels to normal could be a target to prevent or treat dementia, and whether the BRCA1 mutations that increase cancer risk may also affect the brain.

References

  • Suberbielle E, et al. “DNA Repair Factor BRCA1 Depletion Occurs in Alzheimer Brains and Impairs Cognitive Function in Mice.” Nature Communications. November 30, 2015. http://www.nature.com/ncomms/2015/151130/ncomms9897/full/ncomms9897.html.
  • Alzheimer's Disease: Unraveling the Mystery | National Institute on Aging Website. https://www.nia.nih.gov/alzheimers/publication/part-2-what-happens-brain-ad/hallmarks-ad.