Journal Article DZNE-2025-01302

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Serum p‐tau217 Is a Prognostic Indicator of Cognitive Impairment in Idiopathic REM Sleep Behavior Disorder

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2026
Wiley-Blackwell Hoboken, NJ

Annals of neurology 99(4), 912 - 921 () [10.1002/ana.78109]

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Abstract: Assess the performance of serum phosphorylated tau 217 (p-tau217) and neurofilament light chain (NfL) in predicting risk of cognitive impairment or phenoconversion to dementia in individuals with iRBD.We measured serum p-tau217 and NfL levels by electrochemiluminescence across 4 polysomnographically confirmed iRBD cohorts (n = 300), including individuals who phenoconverted to Parkinson's disease (PD) (n = 51), dementia with Lewy bodies (DLB) (n = 22), and multiple system atrophy (MSA) (n = 5).Serum p-tau217 levels were increased in individuals with iRBD and cognitive impairment (CI) on testing defined as Montreal Cognitive Assessment <26 or subthreshold parkinsonism. p-Tau217 differentiated individuals with iRBD who developed PD with CI (PD-CI) or DLB from PD phenoconverters with normal cognition (area under curve [AUC] = 0.82; 95% confidence interval, 0.70-0.93) and from iRBD non-phenoconverters with normal cognition (AUC = 0.83; 95% confidence interval, 0.77-0.89). NfL levels did not correlate with cognitive or motor scores and marginally improved p-tau217 performance (AUC = 0.85; 95% confidence interval, 0.78-0.92), but were notably elevated in iRBD individuals who phenoconverted to MSA. Individuals with p-tau217 in the top quartile were 8 times more likely to phenoconvert to PD-CI or DLB compared to the bottom quartile (hazard ratio = 8.30; 95% confidence interval, 2.49-27.65).Serum p-tau217, but not NfL, is a useful biomarker of cognitive impairment in iRBD that could be integrated into a multimodal prognostic indicator when stratifying risk of phenoconversion. ANN NEUROL 2026;99:912-921.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; tau Proteins: blood (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Cognitive Dysfunction: blood (MeSH) ; Cognitive Dysfunction: diagnosis (MeSH) ; Cognitive Dysfunction: etiology (MeSH) ; REM Sleep Behavior Disorder: blood (MeSH) ; REM Sleep Behavior Disorder: complications (MeSH) ; REM Sleep Behavior Disorder: diagnosis (MeSH) ; REM Sleep Behavior Disorder: psychology (MeSH) ; Prognosis (MeSH) ; Biomarkers: blood (MeSH) ; Middle Aged (MeSH) ; Parkinson Disease: blood (MeSH) ; Parkinson Disease: diagnosis (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Aged, 80 and over (MeSH) ; Lewy Body Disease: blood (MeSH) ; Lewy Body Disease: diagnosis (MeSH) ; Phosphorylation (MeSH) ; Cohort Studies (MeSH) ; Multiple System Atrophy: blood (MeSH) ; Multiple System Atrophy: diagnosis (MeSH) ; Polysomnography (MeSH) ; tau Proteins ; Biomarkers ; Neurofilament Proteins ; neurofilament protein L ; MAPT protein, human

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Contributing Institute(s):
  1. Vascular Neurology (AG Petzold)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025
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 Record created 2025-12-01, last modified 2026-05-11