Stage-dependent associations of glial fibrillary acidic protein and chitinase-3-like protein 1 with white matter network integrity in Alzheimer's disease
Cohort study reveals divergent links between astrocytic biomarkers and white matter integrity in dementia-free older adults, indicating stage-dependent glial responses.
Key Points
To determine how astrocytic reactivity biomarkers GFAP and YKL-40 relate to white matter network integrity, Alzheimer's pathology, and memory across amyloid-β and APOE ε4 risk profiles.
Evaluated 52 dementia-free older adults from the ADNI cohort with longitudinal diffusion tensor imaging and baseline cerebrospinal fluid biomarkers, measuring white matter stability and mean diffusivity within medial temporal lobe networks.
Assessed baseline CSF GFAP, YKL-40, Aβ1-42, p-tau181, APOE ε4 status, and episodic memory, with validation performed using plasma GFAP in an independent Stanford ADRC cohort.
In amyloid-β-negative and APOE ε4-negative individuals, higher CSF GFAP associated with preserved white matter stability and lower mean diffusivity, whereas in amyloid-β-positive and APOE ε4-positive individuals, higher GFAP correlated with elevated p-tau181 instead of white matter preservation.
Elevated CSF YKL-40 consistently associated with reduced white matter network stability regardless of amyloid-β or genetic context.
APOE ε4 carrier status significantly moderated the relationship between plasma GFAP and white matter network integrity in the independent validation cohort.