In France, nearly a million people live with Alzheimer’s disease, while cancer remains the other major age-related threat. In hospitals, however, one observation intrigues doctors: it is rare to see the same patient suffering from both illnesses. This statistical finding recurs from study to study, without a clear explanation, but it fuels speculation that one of the conditions could offer some degree of protection against the other.
When cancer seems to protect against Alzheimer’s disease
A meta-analysis of more than 9.6 million people even showed that a cancer diagnosis was accompanied by an approximately 11% reduction in the risk of Alzheimer’s disease. For a long time, this link was seen as a curious biological coincidence. A Chinese team now claims to have identified a precise mechanism: a small protein from tumors that cleans the brain.
In the brain affected by Alzheimer’s disease, abnormal amounts of a natural protein called beta-amyloid build up to form plaques. These plaques impair communication between brain cells, which gradually leads to cognitive decline and memory loss. Current treatments have difficulty eliminating these clumps. To explore how cancer might offer protection, researchers at Huazhong University of Science and Technology, China, used mice genetically modified to develop beta-amyloid plaques characteristic of Alzheimer’s disease, then implanted them with human tumors from the lungs, colon or prostate.
In these animals suffering from cancer, the amyloid plaques of the brain have decreased significantly.
Cystatin C: the tumor protein that “cleans” the brain
By analyzing the substances released by tumors, the team isolated a key protein: cystatin C (Cyst-C). Produced in large quantities by peripheral cancers, it circulates in the blood, crosses the blood-brain barrier and enters the brain. There, it binds to both the toxic amyloid oligomers and the receptor
TREM2 on the surface of microglia, the immune cells of the brain, which it pushes to digest the plaques already formed. This scenario only works if this cystatin C – TREM2 duo remains intact. When researchers delete TREM2 in microglia (Cx3cr1TREM2-/- mice) or introduce the R47H variant of TREM2, or a mutated form of cystatin C (Cyst-CL68Q), the protective effect disappears.
To verify the concrete impact, the scientists subjected the rodents to an aquatic maze where they had to find a hidden platform. Before, Alzheimer’s mice got lost; after treatment with proteins secreted by tumors or with purified cystatin C, they localized the exit much more quickly.
“Our results provide important conceptual advances in cancer neuroscience and establish therapeutic pathways distinct from current amyloid reduction strategies, aimed at degrading existing amyloid plaques for precision therapy against Alzheimer’s disease.“summarized Youming Lu, lead author of the study.
Towards future treatments against Alzheimer’s?
This work sheds light on why, at the population level, the
cancer protects against Alzheimer’s disease in a modest but measurable way, without offering an individual guarantee. The objective is not to take advantage of tumors, but to reproduce the action of cystatin C by boosting microglia so that they eliminate existing deposits. However, everything remains at the stage of mouse models, and independent specialists point out that it will still take years of studies before considering human trials.