Loss of TREM2 function increases early amyloid buildup but lowers ApoE levels near plaques

Coding variants in TREM2 are associated with late-onset Alzheimer's disease.

• Amyloid plaque seeding increases when Trem2 is not functional.
• Decreased clustering of microglia is observed around newly formed plaques in Trem2 loss-of-function models.
• Reduced deposition of apolipoprotein E (ApoE) in plaques correlates with the presence of TREM2 coding variants in Alzheimer's patients.
• Microglia are identified as a source of plaque-associated ApoE.
• Longitudinal imaging shows accelerated amyloid formation in early stages without functional Trem2, but progression slows with aging.

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