Semantic intrusion errors are associated with plasma Ptau-181 among persons with amnestic mild cognitive impairment who are amyloid positive

INTRODUCTION: Semantic intrusion errors (SI) have distinguished between those with amnestic Mild Cognitive Impairment (aMCI) who are amyloid positive (A+) versus negative (A−) on positron emission tomography (PET). METHOD: This study examines the association between SI and plasma – based biomarkers. One hundred and twenty-eight participants received SiMoA derived measures of plasma pTau-181, ratio of two amyloid-β peptide fragments (Aβ42/Aβ40), Neurofilament Light protein (NfL), Glial Fibrillary Acidic Protein (GFAP), ApoE genotyping, and amyloid PET imaging. RESULTS: The aMCI A+ (n = 42) group had a higher percentage of ApoE ɛ4 carriers, and greater levels of pTau-181 and SI, than Cognitively Unimpaired (CU) A− participants (n = 25). CU controls did not differ from aMCI A− (n = 61) on plasma biomarkers or ApoE genotype. Logistic regression indicated that ApoE ɛ4 positivity, pTau-181, and SI were independent differentiating predictors (Correct classification = 82.0%; Sensitivity = 71.4%; Specificity = 90.2%) in identifying A+ from A− aMCI cases. DISCUSSION: A combination of plasma biomarkers, ApoE positivity and SI had high specificity in identifying A+ from A− aMCI cases.