TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease

Elevated risk of developing Alzheimer's disease is associated with hypomorphic variants of TREM2.

• Microglia in Alzheimer's patients with TREM2 risk variants exhibit an abundance of autophagic vesicles.
• TREM2-deficient mice with Alzheimer's-like pathology also show increased autophagic vesicles.
• Defective signaling through the mammalian target of rapamycin (mTOR) is linked to abnormal autophagy and affects energy levels.
• Restoration of metabolic function and autophagy in vitro was achieved using Dectin-1 and cyclocreatine.
• Dietary cyclocreatine reduced autophagy and improved microglial clustering and neuronal health in TREM2-deficient mice.

AI simplified