Plasma phospho‐tau217 can detect Alzheimer‐like pathology in Parkinson’s disease with dementia and dementia with Lewy bodies

Authors: Sara Hall, Erik Stomrud, Shorena Janelidze, Elisabet Londos, Jeffrey L. Dage, Oskar Hansson

Published: 2020-12-07

Abstract

AbstractBackgroundParkinson’s disease with dementia (PDD) and Dementia with Lewy bodies (DLB) are considered synucleinopathies; however, neuropathology studies have revealed the common occurrence of comorbid Alzheimer’s disease (AD) pathology. Especially AD‐like tau pathology may contribute to cognitive decline in PDD/DLB. In vivo, the presence of co‐pathologies can be detected with PET imaging or CSF testing. However, recent advances in blood biomarkers make it feasible to investigate their utility for identifying AD co‐pathology. In this study we investigate plasma P‐tau217 and P‐tau181 in patients with PDD and DLB.MethodWe included 36 patients with PDD (n = 5) or DLB (n = 31), all part of the BioFINDER 2 study. Plasma was analyzed for P‐tau217 and P‐tau181. Also, CSF was analyzed for P‐tau217, P‐tau181, and Aβ42/Aβ40. 32 patients had undergone [18F]RO940 PET scans to detect AD‐like tau aggregates.ResultPlasma P‐tau217 had significant correlations with plasma P‐tau181 (Rs = 0.683, p < 0.001), CSF P‐tau217 (Rs = 0.678, p < 0.001) and negatively with CSF Aβ42/40 ratio (Rs = ‐0.568, p < 0.001). Both plasma P‐tau217 and plasma P‐tau181 correlated with [18F]RO940 retention in both a temporal meta‐ROI (stage I‐IV) (β= 0.61, p < 0.001 and β = 0.55, p = 0.002) and an extratemporal neocortical meta‐ROI (stage V‐VI) (β = 0.68, p < 0.001 and β = 0.57, p = 0.005). Plasma P‐tau217 predicted [18F]RO940 PET positivity with an AUC = 0.84 using the temporal meta‐ROI (stage I‐IV) and an AUC = 0.92 using the extratemporal neocortical meta‐ROI (stage V‐VI). Furthermore, plasma P‐tau217 predicted [18F]RO940 positivity with a significantly higher accuracy compared with plasma P‐tau181. The performance of plasma P‐tau217 in predicting [18F]RO940 positivity was similar to that of CSF P‐tau217. Additionally, plasma P‐tau217 predicted CSF Aβ positivity with an AUC = 0.91, also with a higher accuracy compared with plasma P‐tau181.ConclusionPlasma P‐tau217 might be a useful marker for AD co‐pathology in PDD and DLB, and may be useful for stratification of patients in clinical trials. Future studies are needed to determine whether plasma P‐tau217 provide important prognostic information in patients with PDD or DLB.