Real‐world utility of plasma GFAP and NfL in early‐onset AD and FTD
Pratishtha Chatterjee, Svetlana Ivanic, Adam Southon, Claire McCarthy, Sheila K. Patel, Maja Christensen, David Darby, Ashley I. Bush, Scott Ayton, Michelle M. Mielke, Emilio Werden, Amy BrodtmannAbstract
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.