Real-world utility of plasma GFAP and NfL in early-onset AD and FTD.

INTRODUCTION: Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are promising blood biomarkers, but their real-world diagnostic utility in early-onset dementia is understudied. METHODS: Plasma GFAP, NfL, and phosphorylated tau (p-tau)217 were measured using Simoa in 118 patients with cognitive complaints, clinically classified as non-neurodegenerative conditions (non-ND; n = 52), early-onset Alzheimer's disease (EOAD; n = 39), frontotemporal dementia (FTD; n = 20), or other-neurodegenerative dementia (ND)/ dementia (n = 7). P-tau217 defined Alzheimer's disease pathology. RESULTS: GFAP was elevated in EOAD compared to non-ND, FTD, and other-ND, and distinguished EOAD from non-ND (area under the curve [95% confidence interval (CI)]: 0.924 [0.871-0.977]) but performed poorly for FTD versus non-ND (0.636 [0.496-0.775]). NfL was most elevated in FTD and EOAD, distinguishing both (FTD: 0.869 [0.778-0.961]; EOAD: 0.770 [0.673-0.867]) from non-ND, but less effective for FTD versus EOAD (0.750 [0.597-0.903]). GFAP appeared stable in severe renal impairment, while NfL increased. DISCUSSION: These findings support integrating GFAP and NfL into clinical dementia assessments, with GFAP offering added diagnostic specificity in cases of severe renal impairment; however, validation in larger cohorts is needed.