Introduction: Lewy body–related pathology is commonly observed at autopsy in individuals with dementia, but in vivo biomarkers for α-synucleinopathy are lacking. Methods: Baseline cerebrospinal fluid (CSF) biomarkers, polygenic risk score (PRS) for Parkinson’s disease (PRS-PD) and Alzheimer’s disease (PRS-AD), longitudinal cognitive scores, and magnetic resonance imaging were measured in 217 participants from the Alzheimer’s Disease Neuroimaging Initiative. Linear mixed models were used to find the relationship of CSF biomarkers and the PRS with cognition and cortical atrophy. Results: Higher PRS-PD and PRS-AD were associated with lower CSF α-synuclein and amyloid beta (Aβ), respectively. Lower CSF α-synuclein and the interaction of CSF α- synuclein and Aβ were associated with lower cognitive scores and global cortical atrophy most prominently in the occipital cortex. Discussion: Lower CSF α-synuclein could be a biomarker for α-synucleinopathy, and the simultaneous evaluation of CSF biomarkers for AD and CSF α-synuclein could reveal the independent and interactive effects on cognition and cortical atrophy.
|Journal||Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring|
|Publication status||Published - 2021|
Bibliographical noteFunding Information:
The authors are grateful to all the participants who have taken part in this study. This research was conducted in collaboration with Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine. Data collection and sharing for this project was funded by ADNI (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research has provided funding to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www. fnih.org/). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was supported by a National Research Foundation of Korea Grant funded by the Korean Government (NRF-2019R1I1A1A01059454), new faculty research seed money grant of Yonsei University College of Medicine (2020-32-0034), and by grants from the Canadian Institute of Health Research awarded to Professor Alan C. Evans (201085 & 247003).
National Research Foundation of Korea, Grant/Award Number: NRF- 2019R1I1A1A01059454; New faculty research seed money grant of Yonsei University College of Medicine, Grant/Award Number: 2020-32-0034; Canadian Institute of Health Research, Grant/Award Numbers: 201085, 247003
© 2021 The Authors.
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Psychiatry and Mental health