Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.

A disease-associated microglial subtype with elevated GPNMB expands with Alzheimer's pathology and depends on TREM2 for neuroprotection.

• Why it matters: Understanding myeloid cell roles in AD is crucial because their functions influence disease progression and potential therapeutic targets remain unclear.
• What they did: Profiling 832,505 human myeloid cells from 1,607 donors across the lifespan revealed six subclasses and identified adaptive changes, including a microglial subtype linked to AD risk and activity.
• The result: This microglial subtype's expansion and activity depend on TREM2, offering mechanistic insights that could guide the development of targeted therapies for aging and AD.