At first glance, Alzheimer’s and cancer seem to have little in common. One gradually destroys memory and cognitive abilities, while the other ravages the body through uncontrolled cell growth. However, scientists at the MUSC Hollings Cancer Center have discovered an unexpected biological link between the two diseases.
Their new study, published in Cancer Research, shows that a protein strongly associated with Alzheimer’s disease can also improve the strength of the immune system. This finding could open up new approaches for the treatment of cancer, neurodegenerative diseases and age-related functional decline.
The Alzheimer’s-Cancer Paradox
For years, researchers have noticed something strange in the population data: People diagnosed with Alzheimer’s seemed to have a much lower risk of developing cancer. This unusual pattern piqued the interest of Dr. Besim Ogretmen, Associate Director of Basic Research at Hollings, who set out with his team to find the biological explanation.
Epidemiologist Dr. Kalyani Sonawane led the effort to verify this link. Her group examined five years of nationally representative survey data and found impressive evidence: Adults over age 59 with Alzheimer’s were 21 times less likely to develop cancer than people without Alzheimer’s. Although the link was clear, the underlying reason was not. What biological mechanism could explain why the two diseases seem to work in opposite directions?
Rejuvenation of the Immune System
Through a series of experiments, the researchers were able to trace the link back to a known culprit: Amyloid-beta, the protein known to form damaging plaques in the brains of Alzheimer’s patients. They discovered that amyloid-beta has a dual personality, depending on where it acts. In the brain it damages neurons, but in the immune system it seems to strengthen immune cells.
To investigate this further, the team transplanted mitochondria from T cells of Alzheimer’s patients into aging T cells from people without the disease. The change was remarkable. “Older T cells started to function like young, active T cells again. This was an incredible discovery because it points to a completely new approach to rejuvenating the immune system.”
The results also showed that amyloid-beta contributes to cancer in another way – by breaking down fumarate, a small molecule produced in the mitochondria during energy production. Fumarate acts like a brake, preventing mitophagy from getting out of control. When fumarate levels drop, cells recycle too many of their healthy mitochondria, leading to a loss of power. “When you deplete fumarate, you increase mitophagy much more,” Ogretmen explained. “Fumarate no longer binds proteins involved in this process, so the proteins become more active and induce more mitophagy. It’s like a reinforcing feedback loop.”
In T cells, fumarate helps to regulate this balance. When the researchers administered fumarate to aging T cells in mice and human tissue, they found lower levels of mitophagy. By preserving their mitochondria, fumarate gave the immune cells more energy to fight cancer. The discovery that fumarate protects aging T cells from excessive loss of mitochondria and enhances their antitumor activity suggests another way to protect immune health.
Far-Reaching Effects on Cancer and Ageing
Together, these findings shed light on why people with Alzheimer’s are less likely to develop cancer – and how this protection could be harnessed. Rather than attacking tumors directly, this research points to a new generation of therapies that recharge the immune system itself. One approach is mitochondrial transplantation, in which older T cells are given fresh, healthy “power plants” to revitalize their protective function in the fight against disease. Another strategy is to maintain or restore fumarate levels to preserve mitochondria and boost the anti-tumor activity of T cells.the potential applications for cancer are manifold.
Revitalizing T cells by transplanting healthy mitochondria could enhance existing treatments such as CAR-T cell therapy. Ogretmen’s group has already filed a patent for this discovery, which underlines its potential as a new form of therapy. Fumarate-based drugs or supplements could further extend the lifespan and energy of older immune cells by preserving their mitochondria. These could be used in conjunction with immunotherapy to maintain the strength of T cells during treatment.
Beyond cancer, these approaches could help to slow down the ageing of the immune system in general. As mitochondria naturally degrade over time, protecting them could help older adults fight infection and stay healthier. Further research into the double-edged effect of amyloid-beta could also shed light on future treatments for neurodegenerative diseases such as Alzheimer’s by finding ways to isolate its protective immune effects without damaging the brain. For Ogretmen, the new findings underscore the power of teamwork and point to the collaboration between Hollings’ research programs in cancer biology, immunology and prevention. “This was a real team effort,” he emphasized. “We are proud of the different disciplines that were brought together to make these discoveries. The research illustrates how discoveries in one area can open unexpected doors in another.”