Plasma Phosphorylated Tau 217 as a Discriminative Biomarker for Cerebral Amyloid Angiopathy

Abstract

BACKGROUND: Blood-based biomarkers may offer a non-invasive approach to diagnose cerebral amyloid angiopathy (CAA), especially in early-stage. We evaluated the ability of plasma phosphorylated tau-217 (p-tau 217) to differentiate CAA from Alzheimer's disease (AD) and deep perforator arteriopathy (DPA). METHODS: Patients with AD (age 73.7 ± 8.1 years), probable CAA (74.8 ± 6.9 years), or DPA (66.1 ± 10.4 years) were enrolled from memory and stroke clinics at a medical center in Taiwan. All participants received amyloid and tau PET scans. Plasma biomarkers were measured via a SIMOA immunoassay platform. The diagnostic utility of p-tau 217 was assessed using ROC analyses and the Youden cutoff. Associations between plasma p-tau 217 and neuroimaging variables in CAA were explored. RESULTS: Patients with CAA had lower plasma p-tau 217 (0.69 ± 0.76 vs. 1.28 ± 0.97 pg/mL, p < 0.001) and a lower p-tau 217/Aβ40 ratio (0.003 ± 0.002 vs. 0.006 ± 0.003, p < 0.001) than the AD group but higher levels than the DPA group (p-tau 217, 0.27 ± 0.13 pg/mL, p = 0.001; p-tau 217/Aβ40, 0.001 ± 0.0005, p < 0.001), although adjustment attenuated the difference in p-tau 217 between CAA and DPA. Plasma Aβ40, Aβ42, and Aβ40/Aβ42 were not significantly different between groups. Plasma p-tau 217 had moderate to good diagnostic utility to differentiate CAA vs. AD (sensitivity, 64.4%; specificity, 89.5%; AUC, 0.809) and CAA vs. DPA (sensitivity, 67.8%; specificity, 100%; AUC, 0.855). In CAA, p-tau 217 significantly correlated with the severity of CAA, amyloid PET signal intensity, and lobar microbleed count (p < 0.001). CONCLUSIONS: Plasma p-tau 217 may represent a non-invasive biomarker for distinguishing cerebral amyloid angiopathy (CAA) from other conditions, including AD and DPA.