Blood-based multimodal biomarker models for differentiating early-onset Alzheimer's disease from frontotemporal dementia: a longitudinal study of early-onset dementia and family members (LEAF) study

초록

Background Plasma phosphorylated tau (p-tau) biomarkers have improved the diagnosis of Alzheimer's disease (AD), but evidence in early-onset populations remains limited. We evaluated the diagnostic performance of plasma p-tau217 and p-tau181 levels in patients with early-onset AD (EOAD) and early-onset frontotemporal dementia (EOFTD).Methods We analyzed 185 patients (EOAD = 150, EOFTD = 35) aged <= 65 years from the LEAF study (2021-2023). Plasma p-tau217, p-tau181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) levels were measured by immunoassays.Results Both plasma p-tau217 (AUC = 0.831) and p-tau181 (AUC = 0.862) levels demonstrated high discriminative performance, with no significant difference between the two p-tau isoforms. P-tau levels were higher in patients with EOAD, whereas NfL levels were higher in EOFTD and were elevated in those with EOAD participants with severe hippocampal atrophy. Adding NfL, GFAP, and APOE epsilon 4 status further improved the discriminative accuracy for differentiating EOAD from EOFTD.Conclusions Plasma p-tau217 and p-tau181 are effective biomarkers for distinguishing biologically defined EOAD from EOFTD. Incorporating NfL, GFAP, and APOE epsilon 4 status further enhances diagnostic accuracy.

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