Criterion and convergent validity of plasma biomarkers in early-onset Alzheimer's disease: Initial findings from LEADS

Alzheimers Dement (Amst). 2026 May 3;18:e70342. doi: 10.1002/dad2.70342. eCollection 2026 Apr-Jun.

ABSTRACT

INTRODUCTION: Despite expanding use of plasma biomarkers for Alzheimer's disease (AD), minimal examination has been undertaken in early-onset AD (EOAD). Prior analyses assessed criterion and convergent validity of common plasma biomarkers in a well-characterized sample with sporadic EOAD. METHODS: Plasma amyloid beta (Aβ) 42/40, tau phosphorylated at threonine 231 (p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light change (NfL) levels were obtained for 189 EOAD, 52 early-onset non-AD (EOnonAD), and 83 cognitively normal (CN) participants. Diagnostic group differences, convergence with imaging biomarkers, and the capacity to predict specific cognitive domains were investigated. RESULTS: After controlling for cognitive status, EOAD participants exhibited more pathologic levels of Aβ42/40, p-tau231, and GFAP relative to EOnonAD participants. However, NfL displayed the greatest sensitivity to non-amnestic cognitive impairment across the sample. DISCUSSION: These results establish criterion and convergent validity of plasma biomarkers in sporadic EOAD and highlight complementary roles that AD-specific and non-specific plasma markers may play across the course of AD care.

PMID:42088846 | PMC:PMC13135914 | DOI:10.1002/dad2.70342