CSF YKL‐40 demonstrates stage‐specific effects of astrocytic reactivity on Alzheimer's Disease pathology

YKL-40 correlations suggest stage-dependent astrocytic responses. A pro-inflammatory Aβ-tau-associated response emerges first, and becomes mostly associated with tau in Aβ+MCI and AD. Additionally, synaptic dysfunction appears closely linked to tau and YKL-40 as AD progresses, with Braak-like patterns emerging on 18F-AV45_YKL-40 images VoxelStats. This suggests tau is the main neurotoxic hallmark in AD, acting in concert with amyloid and astrocytic reactivity. References 1. Ahmad MH, et al. Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer's disease: Rational insights for the therapeutic approaches. J Clin Neurosci. Jan 2019;59:6-11.doi:10.1016/j.jocn.2018.10.034 2. Valiukas Z, et al. Microglial activation states and their implications for Alzheimer's Disease. J Prev Alzheimers Dis. Jan 2025;12(1):100013.doi:10.1016/j.tjpad.2024.100013 3. Jha MK, et al. Microglia-Astrocyte Crosstalk: An Intimate Molecular Conversation. Neuroscientist. Jun 2019;25(3):227-240.doi:10.1177/1073858418783959.