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

doi:10.1038/s41531-022-00317-8

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

Department of Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English
Article number	57
Journal	npj Parkinson's Disease
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41531-022-00317-8
Publication status	Published - 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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10.1038/s41531-022-00317-8

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@article{e9c225a6384d4cd1aaf7e1bcf3fb8342,

title = "Effects of Alzheimer{\textquoteright}s genetic risk scores and CSF biomarkers in de novo Parkinson{\textquoteright}s Disease",

abstract = "Coexisting Alzheimer{\textquoteright}s disease (AD) pathology is common in Parkinson{\textquoteright}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{\textquoteright}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.",

author = "Lee, {Young gun} and Jeong, {Seong Ho} and Mincheol Park and Kang, {Sung Woo} and Kyoungwon Baik and Seun Jeon and Lee, {Phil Hyu} and Sohn, {Young Ho} and Ye, {Byoung Seok}",

note = "Funding Information: PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson{\textquoteright}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: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41531-022-00317-8",

language = "English",

volume = "8",

journal = "npj Parkinson's Disease",

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AU - Lee, Young gun

AU - Jeong, Seong Ho

AU - Park, Mincheol

AU - Kang, Sung Woo

AU - Baik, Kyoungwon

AU - Jeon, Seun

AU - Lee, Phil Hyu

AU - Sohn, Young Ho

AU - Ye, Byoung Seok

N1 - 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).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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

Abstract

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