Amazing stuff!
"Scientists have found a protein made by cancer cells that protects the brain from Alzheimer’s disease in mice — potentially solving a decades-old puzzle about why cancer and Alzheimer’s disease are rarely found in the same person.
When mouse models of Alzheimer’s disease were given a transplant of lung, prostate or colon cancer, they did not develop the plaques characteristic of the brain condition. ... After more than six years of searching, they identified a cancer protein called cystatin C that could infiltrate the brain and flag brain plaques for destruction by the immune system. The breakdown of plaque improved cognitive performance in mice and, if replicated in humans, could form the basis of a new therapy."
From the highlights and abstract:
"Highlights
• Fight Alzheimer’s disease with peripheral cancers via Cyst-C secretion
• Tumor-derived Cyst-C attenuates amyloid pathology of Alzheimer’s disease
• Human Cyst-C binds amyloid oligomers and activates TREM2
• Tumor-derived Cyst-C degrades pre-existing amyloid plaques via TREM2
Summary
Alzheimer’s disease (AD) and cancer are among the most devastating diseases worldwide. Epidemiological data indicate that the incidence of AD significantly decreases in patients with a history of cancer. However, whether and how peripheral cancer may affect AD progression is yet to be studied.
Here, we find that peripheral cancer inhibits amyloid pathology and rescues cognition via secretion of cystatin-c (Cyst-C), which binds amyloid oligomers and activates triggering receptor expressed on myeloid cells 2 (TREM2) in microglia, enabling microglia to degrade the pre-existing amyloid plaques in AD mice. These effects of Cyst-C are abolished by a cell-type-specific deletion (Cx3cr1TREM2−/−) or mutation of TREM2 (TREM2R47H) or Cyst-C (Cyst-CL68Q) in microglia.
Together, these findings provide significant conceptual advances into cancer neuroscience and establish therapeutic avenues that are distinct from the present amyloid-lowering strategies, aiming at degrading the existing amyloid plaques for precision-targeted AD therapy."
Cancer might protect against Alzheimer’s — this protein helps explain why (open access) "A molecule produced by cancer cells can shield the brain from Alzheimer’s disease in mice."
Peripheral cancer attenuates amyloid pathology in Alzheimer’s disease via cystatin-c activation of TREM2 (open access)
Graphical abstract
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