Faulty BRCA1 Gene Carried By Angelina Jolie Linked To Alzheimer's Disease

01/12/2015 11:03 | Updated 01 December 2015

The faulty BRCA1 gene, which is associated with breast and ovarian cancer, is linked to Alzheimer's disease, researchers believe.

Scientists found that depletion of BRCA1 proteins can result in cognitive problems.

They now hope to test whether increasing BRCA1 levels could prevent or reverse neurodegeneration and memory problems.

angelina jolie

BRCA1 is a human gene that produces proteins which help repair damaged DNA. These proteins play a role in ensuring the stability of the cell’s genetic material.

When the gene becomes mutated, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

Angelina Jolie is a carrier of the gene, which resulted in her getting a double mastectomy and having her ovaries and Fallopian tubes removed earlier this year to reduce her risk of developing cancer.

Now, research published in the journal Nature Communications demonstrates that Alzheimer’s disease is associated with a depletion of BRCA1 in neurons.

"BRCA1 has so far been studied primarily in dividing (multiplying) cells and in cancer, which is characterised by abnormal increases in cell numbers," says Elsa Suberbielle, a research scientist at the Gladstone Institutes and co-author of the study.

"We were therefore surprised to find that it also plays important roles in neurons, which don’t divide, and in a neurodegenerative disorder that is characterised by a loss of these brain cells."


BRCA1 helps repair a type of DNA damage known as 'double-strand breaks' that can occur when cells are injured. However in neurons, such breaks can occur even under normal circumstances - for example, after increased brain activity.

The researchers believe that in brain cells, cycles of DNA damage and repair help to facilitate learning and memory. Whereas an imbalance between damage and repair disrupts these functions.

To test their theory, scientists reduced BRCA1 levels in the neurons of mice. This led to an accumulation of DNA damage and neuronal shrinkage. It also caused learning and memory deficits.

Because Alzheimer’s disease is associated with similar neuronal and cognitive problems, the scientists wondered whether the problems might be caused by depletion of BRCA1.

They then conducted a secondary study looking at neuronal BRCA1 levels in post-mortem brains of Alzheimer’s patients.

They found that neuronal BRCA1 levels in the patients were reduced by 65-75%.

To determine what caused the reduction in neuronal BRCA1 levels, researchers treated neurons grown in cell culture with amyloid-beta proteins, which accumulate in the brains of those with Alzheimer's.

These proteins depleted BRCA1 in the cultured neurons, suggesting that they may be an important cause of the faulty DNA repair seen in the brains of deceased Alzheimer's patients.

Researchers demonstrated that accumulation of amyloid-beta in the brains of mice also reduced neuronal BRCA1 levels.

They now want to find out if increasing BRCA1 levels in mice could prevent or reverse neurodegeneration and memory problems.

"Therapeutic manipulation of repair factors such as BRCA1 may ultimately be used to prevent neuronal damage and cognitive decline in patients with Alzheimer’s disease or in people at risk for the disease," says co-author Lennart Mucke, director of the Gladstone Institute of Neurological Disease.

"By normalising the levels or function of BRCA1, it may be possible to protect neurons from excessive DNA damage and prevent the many detrimental processes it can set in motion."

James Pickett, head of research at Alzheimer’s Society, tells HuffPost UK Lifestyle that the research raises interesting questions about the role that the BRCA1 gene plays in the brain.

"But it is too soon to know if this gene is connected to Alzheimer’s disease or any other form of dementia," he adds.

"The BRCA1 gene plays an important role across many different parts of the body by repairing damaged DNA. Particular changes in the gene are linked to the development of some cancers, but the role of BRCA1 highlighted in this study is very different to that which is linked to cancer.

"The research does not draw any links between risk of developing cancer and dementia. Evidence shows that dementia is caused by a complex interplay of genetics, environmental and lifestyle factors.

"Further research into each of these factors will help us to better understand why people develop the condition and help us to find effective treatments."

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