Research Paper|Volume 17, Issue 2|pp 357—364

Carriers of Parkinson’s disease-linked SNCA Rep1 variant have greater non-motor decline: a 4 year follow up study

Aarthi Santhanakrishnan¹, Yi Jayne Tan², Seyed Ehsan Saffari^2,³, Yi Zhao⁴, Ebonne Y.L. Ng⁵, Samuel Y.E. Ng², Nicole S.Y. Chia², Xinyi Choi⁵, Dede Heng⁵, Shermyn Neo², Zheyu Xu², Kay Yaw Tay², Wing Lok Au², Eng-King Tan^5,⁶, Louis C.S. Tan², Adeline S.L. Ng^2,⁶

¹Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
²Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore
³Center for Quantitative Medicine, Duke-NUS Medical School, National University of Singapore, Singapore
⁴Department of Clinical Translational Research, Singapore General Hospital, Singapore
⁵Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore
⁶Neuroscience and Behavioural Disorders, Duke-NUS Medical School, Singapore

* Joint senior authors

Received: April 17, 2024Accepted: January 17, 2025Published: February 3, 2025

https://doi.org/10.18632/aging.206196

Copyright: © 2025 Santhanakrishnan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Alpha-synuclein gene promoter (SNCA Rep1) polymorphism has been linked to Parkinson's Disease (PD) susceptibility and motor symptom severity, but less is known about its longitudinal relationship with non-motor symptom severity. To address this gap, this is the first longitudinal study over 4 years investigating the relationship between Rep1 allele length and non-motor function amongst 208 early PD patients grouped into long (n = 111) vs. short (n = 97) Rep1 allele carriers. Long Rep1 carriers demonstrated faster decline in global cognition (p = 0.023) and increasing apathy (p = 0.027), with greater decline in attention and memory domains (p = 0.001), highlighting the utility of Rep1 polymorphism in stratifying patients at risk of non-motor symptom decline.