Standard hormone therapy treatment used for prostate cancer may be adversely raising the risk of Alzheimer’s disease in men with the cancer, according to a study on Thursday. Androgen deprivation therapy (ADT) is used to treat prostate cancer. It reduces testosterone (the most common androgen), which the cancer needs to grow.
However, as androgen — a key regulator of amyloid metabolism — gets removed with the therapy, more amyloid is left to form the plaques that are a hallmark of Alzheimer’s, explained researchers at the Medical College of Georgia at Augusta University in the US.
“We know that prostate cancer itself also largely affects men over age 65, which is a population that’s already at a higher risk of Alzheimer’s, simply due to their age,” said Qin Wang, director of the Programme for Alzheimer’s Therapeutic Discovery at MCG. But the role of ADT “is not largely understood”, she said, in the paper reported in the journal Science Advances. To understand the link, the team created an animal model with Alzheimer’s disease and cancer. The team then delivered the ADT for eight weeks, while monitoring androgen levels and tumour size; and changes in the blood to look for immune markers. Next, the team developed other animal models — a so-called wild type (without Alzheimer’s or cancer), a group with just Alzheimer’s, and a group with just cancer that received ADT therapy. While there wasn’t any “significant difference in the plaque load” at the end of eight weeks, they did find hyperactivity in “glial cells (that are part of the central nervous system) of the groups with just cancer and the groups treated with ADT”. This indicated inflammation in the brain, Wang said. Further, they found an increase in pro-inflammatory cytokines — small proteins that trigger an increase in inflammation — and a decrease in anti-inflammatory cytokines. This was particularly declined in the animals with Alzheimer’s and cancer that received ADT.
Importantly, the animals’ blood-brain barrier showed significant damage. “The ADT treatment is actually making the blood-brain barrier more permeable. That would explain why there is so much more inflammation in that group,” Wang said. Using a combination of ADT and natalizumab — a drug used to treat multiple sclerosis and Crohn’s disease — the team also treated the mice who had cancer, and those with Alzheimer’s and cancer. The treatment not only reduced the infiltration but subsequently improved the integrity of the blood-brain barrier. The pro-inflammatory cycle was also reduced, while the cognitive function improved.
“We now know that it’s not just about the amyloid plaques. The immune system’s response is the contributing factor here,” Wang said, calling for clinical trials in patients who are undergoing ADT for prostate cancer.
