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Plasma p-tau181, neurofilament light chain and association with cognition in Parkinson’s disease

L. Batzu, S. Rota, A. Hye, A. Heslegrave, D. Trivedi, L. Gibson, C. Farrell, P. Zinzalias, A. Rizos, H. Zetterberg, K. Ray Chaudhuri, D. Aarsland (London, United Kingdom)

Meeting: 2022 International Congress

Abstract Number: 1203

Keywords: ,

Category: Parkinson's Disease: Cognitive functions

Objective: To investigate the association of plasma p-tau181 and NfL with cognitive performance and cognitive progression in PD patients.

Background: Cognitive impairment (CI) is a significant non-motor symptom of Parkinson’s disease (PD)1, and its early identification has important clinical and research implications. Plasma p-tau181 and plasma neurofilament light chains (NfL) are biomarkers of Alzheimer’s-like pathology and neuro-axonal degeneration respectively2, 3. However, their role as biomarkers of cognition in PD has yet to be established.

Method: We assessed the baseline levels of plasma p-tau181 and NfL in a cohort of 136 patients with PD and 63 healthy controls (HC). Forty-seven PD patients were followed up for up to 2 years. Cognitive performance was assessed using Mini Mental State Examination (MMSE). Cross-sectional and longitudinal associations between baseline plasma biomarkers and cognitive progression were investigated using linear regression and linear mixed effects models.

Results: At baseline, plasma p-tau181 concentration was significantly higher in PD subjects compared to HC (p=0.026) (Table 1, Figure 1). In PD patients, higher plasma NfL was associated with lower MMSE score at baseline, after adjusting for age, sex and education (p=0.027). Baseline plasma NfL also predicted MMSE decline over time in the PD group, after adjusting for age, sex and education (p=0.020) (Table 2, Figure 2). No significant association between plasma p-tau181 and either baseline or longitudinal cognitive performance was found.

Conclusion: While the role of p-tau181 as a diagnostic biomarker for PD and its relationship with cognition needs further investigation, plasma NfL may serve as a feasible, non-invasive biomarker of cognitive progression in PD.

Table 1

Table 2

Figure 2

Figure 1

References: 1. Aarsland D, Batzu L, Halliday GM, et al. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers 2021;7:47.
2. Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. The Lancet Neurology 2020;19:422-433.
3. Lin CH, Li CH, Yang KC, et al. Blood NfL: A biomarker for disease severity and progression in Parkinson disease. Neurology 2019;93:e1104-e1111.

To cite this abstract in AMA style:

L. Batzu, S. Rota, A. Hye, A. Heslegrave, D. Trivedi, L. Gibson, C. Farrell, P. Zinzalias, A. Rizos, H. Zetterberg, K. Ray Chaudhuri, D. Aarsland. Plasma p-tau181, neurofilament light chain and association with cognition in Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/plasma-p-tau181-neurofilament-light-chain-and-association-with-cognition-in-parkinsons-disease/. Accessed May 15, 2025.

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