Combined use of plasma p‐tau217, NfL, and GFAP predicts domain‐specific cognitive decline in cognitively unimpaired and MCI individuals

High phosphorylated tau at threonine 217 (p-tau217) alone was associated with declines in semantic/episodic memory, whereas its combination with elevated glial fibrillary acidic protein (GFAP) predicted declines in a wider range of cognitive domains. Elevated neurofilament light chain (NfL) amplifies the cognitive decline already driven by p-tau217 and GFAP. In cognitively unimpaired individuals, subtle domain-specific cognitive declines can be detected when both core and non-core Alzheimer's disease biomarkers are used. Our finding highlights the importance of focusing on vulnerable cognitive domains during early disease where global cognition may appear stable but specific impairments can be masked within composite scores.