BRCA1 and Alzheimer’s

Protective BRCA1 protein levels are lower in the brains of individuals with Alzheimer’s. Nature Communications, 11/2015.

Sufficient BRCA1 proteins in the brain protect against DNA damage, and physiological neuronal activation increases BRCA1 production.
Interesting research out of Nature Communications demonstrated that in the brains of Alzheimer’s patients, there is a reduction of the protective BRCA1 proteins. Amyloid-beta overexpression was shown to reduce BRCA1 in neuronal cultures. Further, increased stimulation of excitotoxic NDMA receptors was also shown to promote the proteasomal degradation of BRCA1.

The authors conclude that “BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.”

In functional medicine, we’re thinking about neuronal excitoxicity all of the time and how to protect against it. Many of us routinely measure quinolinic acid in our patients, understanding that it’s an inflammatory brain neurotoxin. QUIN specifically revs up the glutamatergic NMDA receptors, depletes local microglial cell glutathione and disrupts CNS neuronal plasticity. QUIN elevation has been implicated in neurodegenerative, neuropsychiatric and neurodevelopmental diseases including Alzheimer’s, Parkinson’s depression and autism. INF-gamma potently upregulates QUIN.

In QUINs role as potent NMDA agonist, it’s likely involved in depleting protective CNS BRCA1 levels, too.

The take-home here is clear: reducing total body inflammation (and therefore INF-gamma) protects the brain.

Tags: BRCA1 and Alzheimer’s

Author: Kara Fitzgerald, ND

https://www.drkarafitzgerald.com/

Kara Fitzgerald, ND, received her doctor of naturopathic medicine degree from the National University of Natural Medicine in Portland, Oregon. She completed the first Counsel on Naturopathic Medicine-accredited post-doctorate position in nutritional biochemistry and laboratory science at Metametrix Clinical Laboratory under the direction of Richard Lord, PhD. Her residency was completed at Progressive Medical Center, a large, integrative medical practice in Atlanta, Georgia. Dr. Fitzgerald is the lead author and editor of Case Studies in Integrative and Functional Medicine and is a contributing author to Laboratory Evaluations for Integrative and Functional Medicine and the Institute for Functional Medicine (IFM)’s Textbook for Functional Medicine. With the Helfgott Research Institute, Dr. Fitzgerald is actively engaged in clinical research on the DNA methylome using a diet and lifestyle intervention developed in her practice. The first publication from the study focuses on reversal of biological aging and was published 04-12-2021 in the journal Aging. She has published a consumer book titled Younger You as well as a companion cookbook, Better Broths and Healing Tonics and has an application-based Younger You Program, based on the study. Dr. Fitzgerald is on the faculty at IFM, is an IFM Certified Practitioner and lectures globally on functional medicine. She runs a Functional Nutrition Residency program, and maintains a podcast series, New Frontiers in Functional Medicine and an active blog on her website, www.drkarafitzgerald.com. Her clinical practice is in Sandy Hook, Connecticut. Additional publications

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The take-home here is clear: reducing total body inflammation (and therefore INF-gamma) protects the brain.

Author: Kara Fitzgerald, ND

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