Effects of Alzheimer’s genetic risk scores and CSF biomarkers in de novo Parkinson’s Disease

Young gun Lee, Seong Ho Jeong, Mincheol Park, Sung Woo Kang, Kyoungwon Baik, Seun Jeon, Phil Hyu Lee, Young Ho Sohn, Byoung Seok Ye

Research output: Contribution to journalArticlepeer-review


Coexisting Alzheimer’s disease (AD) pathology is common in Parkinson’s disease (PD). However, the implications of genetic risk scores (GRS) for AD have not been elucidated in PD. In 413 de novo PD and 195 healthy controls from the Parkinson’s Progression Marker Initiative database, the effects of GRS for AD (GRS-AD) and PD (GRS-PD) on the risk of PD and longitudinal CSF biomarkers and clinical outcomes were explored. Higher GRS-PD and lower baseline CSF α-synuclein were associated with an increased risk of PD. In the PD group, GRS-AD was correlated positively with CSF p-tau/Aβ and negatively with CSF α-synuclein. Higher GRS-PD was associated with faster CSF p-tau/Aβ increase, and GRS-AD and GRS-PD were interactively associated with CSF α-synuclein. In the PD group, higher GRS-AD was associated with poor visuospatial function, and baseline CSF p-tau/Aβ was associated with faster cognitive decline. Higher GRS-PD was associated with better semantic fluency and frontal-related cognition and motor function given the same levels of CSF biomarkers and dopamine transporter uptake. Taken together, our results suggest that higher GRS-AD and CSF p-tau/Aβ, reflecting AD-related pathophysiology, may be associated with cognitive decline in PD patients.

Original languageEnglish
Article number57
Journalnpj Parkinson's Disease
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and funding partners, including Abbvie, Acurex Therapeutics, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, BIAL Biotech, Biogen, BioLegend, Bristol Myers Squibb, Celgene, Denali, 4D Pharma PLC, GE Healthcare, Genentech, GlaxoSmithKline, Golub Capital, Handl Therapeutics, insitro, Janssen Neuroscience, Lilly, Lundbeck, Merck, Meso Scale Discovery, Neurocrine Biosciences, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. This study was supported by the Korean Health Technology R&D Project through the Korea Health Industry Development Institute and Korea Dementia Research Center, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant HU20C0511020021).

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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