Objective: We assess: 1) if the diagnostic accuracy of plasma pTau181 differs from pTau217 in detecting amyloidosis (Aβ) in people with Lewy body disease (LBD) and with alpha-synuclein positivity (aSyn+), 2) LBD-specific cut-offs for plasma pTau181 and pTau217, and 3) the association between plasma pTau181 and pTau217 with CSF Alzheimer’s disease (AD) biomarkers in LBD.

Background: LBD often presents with concomitant Aβ, influencing disease progression. Novel plasma biomarkers plasma pTau181 and pTau217 reliably detect Aβ deposition. Yet, few studies have investigated their utility in LBD or aSyn+ participants. LBD-specific cut-offs for these biomarkers have yet to be defined.

Method: We included 230 Stanford research participants: 110 cognitively normal (CN), 43 LBD-cognitively normal (LBD-CN, i.e. cognitively normal-PD), 41 LBD with cognitive impairment (LBD-CI), and 36 AD. Plasma pTau181 and pTau217 were measured with the Lumipulse G platform and the ALZpath pTau217 assay, respectively. ASyn+ was assessed in CSF with SYNTap®. ROC curve analyses determined the diagnostic accuracy of pTau181 and pTau271 in detecting Aβ+ (determined by CSF Aβ42/40 or Aβ PET); DeLong tests compared model performance. The Youden index determined optimal cut-offs. Spearman’s correlations determined associations between plasma pTau181 and pTau217 with CSF AD biomarkers.

Results: Plasma pTau181 and pTau217 had similar diagnostic accuracy for distinguishing Aβ+ from Aβ- in the LBD groups (Figure 1). However, in a sensitivity analysis, plasma pTau217 outperformed pTau181 in detecting Aβ+ among aSyn+ participants (pTau217 AUC=0.88, 95%-CI: 0.77-1 vs pTau181 AUC=0.77, 95%-CI: 0.64-0.90, p=0.045) (Figure 2). For both biomarkers, LBD-specific cut-offs for Aβ+ differed from AD-specific cut-offs (Figure 3). In the LBD-CI group, both plasma markers were associated with CSF pTau181, Aβ42/40, and pTau181/Aβ42 (Figure 4B). Only plasma pTau217 correlated with CSF Aβ42 in the LBD-CI group, and with CSF pTau181, Aβ42/40, and pTau181/Aβ42 in the LBD-CN group. There were no associations between plasma pTau181 and CSF AD biomarkers in the LBD-CN group (Figure 4A).

Conclusion: Our findings showed that plasma pTau181 and pTau217 can detect Aβ+ in LBD. Particularly, plasma pTau217 seems to be more sensitive for detecting Aβ+ in people with aSyn+. We showed that these biomarkers have LBD-specific cut-offs and distinct associations with CSF AD biomarkers.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-ptau181-and-ptau217-detect-amyloid-co-pathology-and-have-specific-cut-offs-in-lewy-body-disease/