Nature communications · 2025
Glial reactivity correlates with synaptic dysfunction across aging and Alzheimer's disease.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Rohden Francieli, Ferreira Pamela C L, Bellaver Bruna, Ferrari-Souza João Pedro, Aguzzoli Cristiano S, Soares Carolina, Abbas Sarah, Zalzale Hussein, Povala Guilherme, Lussier Firoza Z, Leffa Douglas T, Bauer-Negrini Guilherme, Rahmouni Nesrine, Tissot Cécile, Therriault Joseph, Servaes Stijn, Stevenson Jenna, Benedet Andrea L, Ashton Nicholas J, Karikari Thomas K, Tudorascu Dana L, Zetterberg Henrik, Blennow Kaj, Zimmer Eduardo R, Souza Diogo, Rosa-Neto Pedro, Pascoal Tharick A
Аннотация
Previous studies suggest glial and neuronal changes may trigger synaptic dysfunction in Alzheimer's disease (AD), but the link between their markers and synaptic abnormalities in the living brain remains unclear. We investigated the association between glial reactivity and synaptic dysfunction biomarkers in cerebrospinal fluid (CSF) from 478 individuals in cognitively unimpaired (CU) and cognitively impaired (CI) individuals. We measured amyloid-β (Aβ), phosphorylated tau (pTau181), astrocyte reactivity (GFAP), microglial activation (sTREM2), and synaptic markers (GAP43, neurogranin). CSF GFAP levels were associated with presynaptic and postsynaptic dysfunction, independent of cognitive status or Aβ presence. CSF sTREM2 levels were related to presynaptic markers in cognitively unimpaired and impaired Aβ+ individuals, and to postsynaptic markers in cognitively impaired Aβ+ individuals. Notably, CSF pTau mediated the relationships between GFAP or sTREM2 and synaptic dysfunction. Our findings, validated in two independent cohorts (TRIAD and ADNI), reveal a distinct pattern of glial contribution to synaptic degeneration.