Plasma p-tau181, Aβ1-42, and GFAP across Alzheimer's disease, mixed-type Alzheimer's disease, mild cognitive impairment, anxiety disorders, and depressive disorders.

BACKGROUND

Blood-based biomarkers including phosphorylated tau181 (p-tau181), amyloid β1-42 (Aβ1-42), and glial fibrillary acidic protein (GFAP) have been widely investigated for Alzheimer's disease (AD) detection. However, their utility for discriminating neurodegenerative cognitive impairment from anxiety and depressive disorders remains poorly established.

AIMS: To compare plasma p-tau181, Aβ1-42, and GFAP concentrations across clinically-defined patient groups with AD, mixed-type Alzheimer's disease (MAD), mild cognitive impairment (MCI), anxiety disorders (ANX), and depressive disorders (DEP), and to explore their discriminative performance within this cohort.

METHODS

We recruited 287 participants: AD (n = 80), MAD (n = 41), MCI (n = 54), ANX (n = 53), and DEP (n = 59). Plasma concentrations of p-tau181, Aβ1-42 and GFAP were quantitatively measured using magnetic microparticle chemiluminescence immunoassay. We evaluated inter-group biomarker differences as well as associations between biomarker levels and cognitive performance.

RESULTS

Plasma p-tau181, Aβ1-42, and GFAP concentrations differed significantly across the five diagnostic groups. In the pooled cohort, all three biomarkers showed inverse associations with MMSE scores, although within-group correlations were weaker and inconsistently significant across diagnostic subgroups. ROC analyses showed that p-tau181 and GFAP had numerically higher AUC values than Aβ1-42 in several pairwise comparisons involving AD or MAD and other clinical groups.

CONCLUSIONS

Plasma p-tau181, Aβ1-42, and GFAP showed distinct concentration profiles across the clinically-defined diagnostic groups in this exploratory cross-sectional cohort. GFAP and p-tau181 showed moderate-to-good discriminative performance in several pairwise comparisons involving AD or MAD, whereas Aβ1-42 showed comparatively lower standalone discriminative performance.