Stage-Specific Roles of Plasma GFAP in Linking Amyloid Cascade in Alzheimer Disease

Plasma GFAP mediates links between soluble Abeta42/40 and amyloid PET, and between amyloid PET and tau PET, across Alzheimer disease biomarker cohorts (n=278; n=236).

• Why it matters: Astrocytic reactivity is elevated throughout the AD continuum, but how plasma GFAP relates to the amyloid cascade and downstream tau pathology is unclear.
• What they did: The study integrated plasma GFAP with CSF or plasma Abeta42/40, amyloid and tau PET, structural MRI, and clinical severity in a discovery cohort (Knight ADRC, n=278) and replication cohort (ADNI, n=236), testing mediation within A/T-defined groups.
• The result: Mediation remained significant after false discovery rate correction overall, with subgroup significance limited to Knight ADRC for tau-negative soluble Abeta42/40→amyloid PET and to ADNI for amyloid-positive amyloid PET→tau PET; proteomics revealed a GFAP-associated extracellular matrix and immune pathway network.

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