Objective: Plasma neurofilament light (NfL; a marker of axonal injury) and phosphorylated tau 181 (pTau181) are biomarkers that have been associated with cognitive decline in Alzheimer’s disease and mild cognitive impairment. Carriers of long SNCA Rep1 alleles and APOE4 have increased risk of Parkinson’s disease (PD) dementia. Little is known about the interaction between the genetic factors of SNCA Rep1 and APOE4 with the blood biomarkers of NfL and pTau181 in PD.
Background: To address this gap, we investigated these longitudinal associations in a cohort of early PD patients.
Method: 207 patients with PD (disease duration ≤ 1 year) and 64 healthy controls (HC) were included. Patients were genotyped and grouped according to APOE4 and Rep1 status (long vs short allele carriers). Plasma NfL and pTau181 were measured using single molecule array (Simoa). Associations between biomarkers, genetic risk factors and longitudinal change in cognitive domain outcomes (memory, attention, language, visuospatial and executive function) were analysed, controlling for age, gender, disease duration and education.
Results: At baseline, NfL and pTau181 were not significantly different between PD and HC, but correlated with each other in HC (rs= 0.303, p=0.013) and PD (rs= 0.333, p<0.001). Over 5 years, significant interaction was found in PD cases carrying both APOE4 and long Rep1 alleles: higher baseline NfL was associated with greater decline in MMSE (p=0.024), MoCA (p=0.003), language (p=0.012), and executive domains (p=0.015), and higher baseline pTau181 with greater decline in MMSE (p=0.002), MoCA (p=0.005), and executive domains (p=0.045) when compared to other genetics groups (non-carriers APOE4 or short Rep1), controlling for potential confounders.
Conclusion: In this longitudinal study over 5 years, we demonstrated for the first time the interaction of plasma NfL and pTau181 with known genetic risk factors are associated with accelerated global and domain‐specific cognitive decline in early PD patients carrying both APOE4 and long SNCA Rep1 alleles. These findings indicate that plasma NfL and ptau181 may be useful biomarkers in detecting risk of cognitive decline and allowing for early intervention for genetically-at-risk patients.
To cite this abstract in AMA style:
S. Ng, J. Tan, E. Saffari, E. Ng, X. Choi, D. Heng, S. Neo, Z. Xu, K. Tay, W. Au, E. Tan, L. Tan, A. Ng. Baseline plasma neurofilament light and phosphorylated tau 181 levels predict longitudinal cognitive decline in APOE4 and long SNCA Rep1 carriers in Parkinson’s disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/baseline-plasma-neurofilament-light-and-phosphorylated-tau-181-levels-predict-longitudinal-cognitive-decline-in-apoe4-and-long-snca-rep1-carriers-in-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/baseline-plasma-neurofilament-light-and-phosphorylated-tau-181-levels-predict-longitudinal-cognitive-decline-in-apoe4-and-long-snca-rep1-carriers-in-parkinsons-disease/