How Reactivity of Astrocytes and Microglia Relates to Amyloid and Tau Proteopathy
Microglia and astrocytes become more reactive in the aging brain, leading to sustained inflammation that contributes to neurodegenerative conditions. Research indicates distinct mechanisms driving astrocyte and microglia reactivity. In Alzheimer’s disease, microglial inflammation is linked to amyloid-β and tau protein pathology, creating a feedback loop of inflammation and pathological tau. Glial reactivity is associated with synaptic dysfunction in AD, with tau phosphorylation playing a key role. These findings suggest synaptic biomarkers could be used in clinical trials targeting glial reactivity.
Previous studies highlight the connection between glial reactivity, neuronal changes, and synaptic dysfunction in AD. A study explored the association between biomarkers of astrocyte and microglial reactivity and synaptic dysfunction in individuals across the aging and AD spectrum. Results showed elevated GFAP levels were linked to presynaptic and postsynaptic dysfunction, while sTREM2 levels were associated with synaptic biomarkers. CSF pTau181 levels mediated the associations between glial reactivity biomarkers and synaptic dysfunction. These findings support synaptic biomarkers as potential secondary endpoints for clinical trials targeting glial reactivity in aging and AD.
