Category: MSA, PSP, CBS (Other)
Objective: We aim to elucidate the genetic architecture of progressive supranuclear palsy (PSP) in East Asians through whole-exome sequencing in a multi-center study in Taiwan.
Background: PSP is a parkinsonism-plus syndrome characterized by vertical supranuclear gaze
palsy, early falls, parkinsonism, and dementia and the neuropathological features are 4 repeat tau deposition within neurons. While PSP is mostly sporadic, recent evidence shows both common and rare genetic variants contribute to its pathogenesis Population-specific studies are vital for identifying novel risk variants, especially in the current era of precision medicine. However, the genetic architecture of PSP in East Asian populations remains largely unexplored.
Method: We recruited 177 PSP patients from a Taiwanese cohort and performed whole-exome sequencing to identify potentially pathogenic variants. As a reference cohort, we used whole-genome sequencing data from 1492 asymptomatic individuals in the Taiwan Biobank. To evaluate the mutation burden in MAPT and LRRK2, we compared the genetic data of PSP patients with this ethnicity-matched control cohort.
Results: We identified three likely pathogenic variants, including variants in APP, ABCA7, and the homoplasmic mitochondrial 4300A>G mutation in three sporadic PSP patients (1.69%).. In addition, we discovered 39 different variants of unknwon significance with high pathogenicity scores in 37 PSP patients (20.9%), involving genes such as MAPT, LRRK2, STX6, EIF2AK3, BSN, LRP10, APP, ABCA7, DNAJC13, CHCHD10, PRNP, PSEN1, PSEN2, TMEM106B, VPS35, and SQSTM1. In addition, a higher loads of MAPT and LRRK2 were observed in PSP patients compared to the control group (p <0.0001).
Conclusion: The genetic architecture of PSP in East Asian patients appears to differ from Western populations The increased mutation load of MAPT and LRRK2 in PSP further strengthen the potential interaction between LRRK2 and tau in the process of PSP..
MAPT mutation load
LRRK2 mutation load
To cite this abstract in AMA style:
P. Chen, R. Lin, N. Lee, J. Hsu, C. Tai, R. Wu, H. Chiang, Y. Wu, C. Lu, H. Chang, T. Lee, Y. Chang, C. Lin. Unraveling the Genetic Architecture of Progressive Supranuclear Palsy in East Asians [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/unraveling-the-genetic-architecture-of-progressive-supranuclear-palsy-in-east-asians/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/unraveling-the-genetic-architecture-of-progressive-supranuclear-palsy-in-east-asians/