Reduced TREM2 Levels in Mice and Humans Weaken Brain Immune Cells’ Barrier, Leading to Less Dense Amyloid and Worse Nerve Damage

Haplodeficiency of the TREM2 gene is linked to increased risk for late-onset Alzheimer's disease.

• Microglia processes containing TREM2 tightly encircle early amyloid fibrils and plaques, facilitating their compaction.
• In models with reduced TREM2, microglia show decreased ability to envelop amyloid deposits.
• This deficiency results in less compact plaques characterized by longer and branched amyloid fibrils.
• Greater surface exposure of amyloid to nearby neurites is observed in these conditions.
• Severe neuritic tau hyperphosphorylation and axonal dystrophy occur around amyloid deposits in the absence of TREM2.
• Disruption of a protective microglia barrier by TREM2 deficiency may affect amyloid regulation.

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