Study: Study uses mice and brains from deceased Alzheimer’s patients to assess BRCA1 involvement

IN DEPTH REVIEW OF RESEARCH

Study background:

BRCA1 and BRCA2 are involved in repairing errors in DNA. Researchers have seen lots of DNA damage in brains cells of patients with Alzheimer’s disease. Lennart Mucke, M.D and colleagues at the Gladstone Institute of Neurological Disease and the University of California, San Francisco want to understand what DNA repair mechanisms might be involved in that damage. Although DNA damage is not known to cause Alzheimer’s disease, it is seen in Alzheimer’s patients and may be an effect of the disease.

Researchers of this study wanted to know:

Whether the DNA damage seen in the neurons of patients with Alzheimer’s could be explained by lower levels of BRCA1 protein.

Population(s) looked at in the study:

For the experiments looking at the BRCA1 levels in brains from deceased patients, researchers examined the brains of 8 patients without Alzheimer’s disease and 8 patients with Alzheimer’s disease.

Mice studies were also made:

• mice that were genetically engineered to have some Alzheimer’s disease symptoms.
• mice that were engineered to have less BRCA1 protein.

Each treatment group included 3 to 20 mice for the various experiments. 

Study findings: 

1. Mice that do not have BRCA1 protein in their neurons have more DNA damage, smaller neurons and have deficiencies in learning and memory.
2. Brains from deceased Alzheimer’s disease patients have lower BRCA1 protein levels.

Limitations:

The number of patient samples used was small: 8 samples for each group. Most of the experiments were performed in mice, however, test results from mice do not conclusively indicate what will occur in humans. Importantly, the study only reviewed normal BRCA1 genes and not BRCA1 mutations associated with increased cancer risk. 

Conclusions:

While the studies looking at mice without BRCA1 protein appear convincing regarding a potential role for BRCA1 in neuronal function, no published study has associated BRCA1 with Alzheimer’s disease.  For many years, researchers have been looking for genetic factors that increase the risk of Alzheimer’s disease—BRCA1 is not a gene that is associated with the disease. More importantly, no clinical data show that people with BRCA1 mutations have an increased risk for developing Alzheimer’s.

Some media headlines claim that BRCA1 mutations may affect Alzheimer’s disease, but this cannot be concluded from the study. Everybody is born with 2 copies of the BRCA1 gene. People with BRCA1 mutations have one "bad copy" (the one with the mutation) and one "normal copy.” This Alzheimer’s disease study looked at how normal copies of BRCA1 work in people with Alzheimer's disease, not how BRCA1 mutations affect Alzheimer’s disease.   

According to the National Institute on Aging, Alzheimer’s disease is the most common form of age-related dementia in the United States.  Given how common Alzheimer’s disease is—over 5 million Americans currently live with the disease—it is likely that some families will be affected by both BRCA1 mutations and Alzheimer’s disease, but that does not mean that the two are associated. 

For now, the reduced levels of BRCA1 in Alzheimer’s patients observed by researchers is only an observation that does not conclude anything about the effects of BRCA1 mutations on the disease.  More research needs to be done to understand the role of normal BRCA1 proteins in Alzheimer’s disease, but based on current research there is no reason to believe that BRCA1 mutations carriers are at increased risk of Alzheimer’s disease.