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. 2025 Feb;32(2):e70066.
doi: 10.1111/ene.70066.

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

Pei-Feng Hsieh  1   2   3 , Hsin-Hsi Tsai  1 , Chia-Ju Liu  4 , Bo-Ching Lee  5 , Ya-Chin Tsai  6 , Ruoh-Fang Yen  4 , Jiann-Shing Jeng  1 , Li-Kai Tsai  1
Affiliations

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

Pei-Feng Hsieh et al. Eur J Neurol. 2025 Feb.

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.

Keywords: Alzheimer disease; cerebral amyloid angiopathy; cerebral small vessel disease; phosphorylated tau 217; plasma biomarker.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of enrollment in this study. Fifty‐nine probable cases of CAA were identified (25 patients with cognitive impairment and 34 survivors of ICH). Additionally, 19 patients with AD and 22 patients with DPA were included as comparison groups.
FIGURE 2
FIGURE 2
Levels of plasma biomarkers in AD, CAA, and DPA. Box plots and scatter plots of (A) p‐tau 217, (B) p‐tau 217/Aβ40, and (C) p‐tau 217/Aβ42 in the AD, CAA, and DPA groups. Red diamonds represent the means. The boxes encompass 50% of the samples, and the whiskers extend 1.5 quartiles to each side of the box. Significant differences are indicated, including p‐values.
FIGURE 3
FIGURE 3
Diagnostic performance of the plasma biomarkers. Receiver‐operating characteristic curves (ROC) of Aβ40, Aβ42, p‐tau217, p‐tau 217/Aβ40, and p‐tau 217/Aβ42 for differentiation of (A) CAA vs. AD and (B) CAA vs. DPA. Compared to plasma beta amyloid alone, p‐tau 217 and the composite biomarkers (p‐tau 217/Aβ40 and p‐tau 217/Aβ42) had much larger areas under the curve (AUC) for CAA vs. AD and CAA vs. DPA.
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