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Cancer Protein Cystatin‑C Triggers Amyloid Clearance in Alzheimer’s Mouse Models

The Cell study reports that cystatin‑C from certain tumors activated microglia via TREM2 to clear amyloid in mouse brains.

Overview

  • University of Toronto researchers report in Cell that tumor‑secreted cystatin‑C bound small amyloid clusters and promoted their removal in Alzheimer’s mouse models.
  • Disabling the cystatin‑C pathway eliminated the plaque‑reducing effect, identifying a necessary mechanism involving microglial activation through TREM2.
  • Mice carrying implanted human lung, prostate, or colon tumors accumulated fewer amyloid plaques, and some experiments showed improved memory performance.
  • The findings offer a potential biological explanation for epidemiological data showing a lower co‑occurrence of cancer and Alzheimer’s, though not all cancers produce cystatin‑C.
  • Experts caution the results are preliminary and in animals, highlighting the need to confirm activity and safety in humans and to explore therapies that mimic this pathway without inducing cancer.