Using plasma ptau181 in Lewy Body Disease spectrum for the identification of Alzheimer’s disease co‐pathology

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Abstract Background Lewy body disease (LBD) patients frequently present with Alzheimer’s disease (AD) co‐pathology, which influences disease progression, cognitive decline, and brain atrophy. AD‐related pathology can be identified with new blood‐based biomarkers like plasma phosphorylated‐tau181 (ptau181). We aimed to determine whether plasma ptau181 helps identify AD‐related co‐pathology in LBD, and whether plasma ptau181 is associated with clinical features, and AD cerebrospinal (CSF) biomarkers. Method From a total of 632 Stanford research participants, we selected 245: 115 cognitively normal (CN), 47 Parkinson’s disease (PD) with normal cognition, 47 on the LBD spectrum (31 MCI and 16 dementia), and 36 on the AD spectrum (14 MCI and 22 dementia). Plasma ptau181 levels were measured with Lumipulse G fully automated platform by Fujirebio with Lumipulse G Assays. A subset of the participants had available AD CSF biomarkers (N = 201) and/or 18F‐Florbetaben PET imaging (N = 73). Diagnostic accuracy was evaluated with area‐under‐the‐curve (AUC) values from receiver‐operating characteristic (ROC) analyses. Linear regression models adjusted for confounding factors were used to analyze effects of baseline plasma ptau181 levels on global cognition (MoCA), global function (CDR‐SOB), motor function (UPDRS Part III), and functional disability (Hoehn and Yahr). Result Plasma ptau181 levels were higher in the LBD spectrum group compared to CN and PD with normal cognition groups, but lower than in the AD spectrum group. Plasma ptau181 levels predicted CSF ptau181/Aβ42 ratio in LBD spectrum patients with an AUC = 0.87. Including age, sex, years of education, and APOE E4 genotype levels improved the prediction of the model (AUC = 0.94). In the LBD spectrum group, males and females showed similar plasma ptau181 levels, and we found no association between plasma ptau181 levels with age, sex, years of education, MoCA, CDR‐SOB, UPDRS Part III, or Hoehn and Yahr. Nevertheless, plasma ptau181 levels were associated with CSF ptau181 levels and amyloid‐β42/40 after controlling for age and sex. Conclusion Plasma ptau181 levels help identify LBD patients with AD co‐pathology, and are associated with AD CSF biomarkers. These findings support the use of plasma ptau181 as a screening tool for AD co‐pathology in patients with LBD and cognitive impairment.

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