Lan G, Chen X, Yang J, Sun P, Cai Y, Li A, Zhu Y, Liu Z, Ma S, Guo T, Alzheimer's Disease Neuroimaging Initiative. Microglial Reactivity Correlates with Presynaptic Loss Independent of β-Amyloid and Tau. Ann Neurol. 2024 May;95(5):917-928. Epub 2024 Feb 14 PubMed.
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Shenzhen Bay Laboratory
In this study, we found that higher baseline levels of CSF microglial biomarkers were related to faster rates of CSF sTREM2 increase and CSF PGRN decrease. Elevated CSF p-Tau181 was associated with higher levels of CSF microglial biomarkers and faster rates of CSF sTREM2 increase and CSF PGRN decrease based on the ADNI cohort.
We repeated part of these analyses in a Chinese Aging cohort (GHABS). In both cohorts, higher Aβ burden was associated with attenuated CSF p-Tau181 effects on CSF microglial biomarker increases. Independent of Aβ PET and CSF p-Tau181 pathologies, higher levels of CSF sTREM2 but not CSF PGRN were related to elevated CSF GAP-43 levels and faster rates of CSF GAP-43 increase.
These findings suggest that higher Aβ burden may attenuate the p-Tau-associated microglial responses, and TREM2-related microglial reactivity may independently correlate with GAP-43-related presynaptic loss. This study highlights the two-edged role of microglial reactivity in AD and other neurodegenerative diseases.
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