In both Alzheimer’s disease and all cancers in general, the pathophysiological mechanism has not yet been clearly identified and understood. Women in their sixties are about twice as likely to develop Alzheimer’s disease over the rest of their lives as they are likely to develop breast cancer. Unfortunately, many women worldwide suffer from either breast cancer or Alzheimer’s or, in the worst cases, both.
For many years, it has been known that the BRCA1 (Breast Cancer 1) gene is significant in breast and ovarian cancers. BRCA1 is a human tumor suppressor gene (a caretaker gene) that specializes in repairing DNA. The gene is normally present in breast cells but is also found in other tissues, where it focuses on repairing damaged DNA or, if necessary, destroying the cells in the DNA that cannot be repaired. The gene itself is normal, and its mutation is abnormal and cancerous. Statistics show that, out of the women who inherit a harmful BRCA1 mutation, 55 to 65 percent will develop breast cancer and 39 percent will develop ovarian cancer by the age of seventy.
Alzheimer’s, the most common form of dementia, is a neurodegenerative disease characterized by the death of neurons and loss of brain tissue. Initial symptoms tend to be quite moderate, but they gradually increase and become more severe, with the earliest and most common being memory lapses.
Since 1994, scientists have known that mutations in the aforementioned gene lead to higher risks of developing cancers, but it has recently been discovered that the gene may also play a part in the nerve death that’s responsible for Alzheimer’s disease. It is surprising to see that a gene that was primarily studied in cancerous cells is linked to the nerve cell death which caused Alzheimer’s disease.
The director of the Gladstone Institute of Neurological Disease, Lennart Mucke, MD discovered that BRCA1 levels in autopsy brains of humans who have died with Alzheimer’s were up to 75 percent lower than those in the brains of people without Alzheimer’s. Mucke has also investigated this using human amyloid precursor protein (hAPP) transgenic mice, where he found reduced BRCA1, just like in the post-mortem Alzheimer’s patients. The reduction of the gene in mice led to an increase in the amount of damaged DNA, as well as an increase in neuronal shrinkage. Additional effects include learning and memory deficits, which are often encountered in patients with Alzheimer’s disease.
One of the reasons why Alzheimer’s disease and cancer seem to be inversely associated is due to both diseases arising via the malfunction of a similar underlying mechanism that regulates cell survival. This supposed mechanism could regulate the ability of the cells to switch the cell machinery from a prone-to-death state, which is the phenotype of Alzheimer’s disease, to a prone-to-survival and/or growth state, which is the cancerous phenotype. It is surprising that the same molecule is so strongly involved in two different and ‘contradicting’ conditions.
Edited by: Daryn Dever