Distinct metabolic signatures of Alzheimer’s and Parkinson’s disease revealed through genetic overlap with metabolic markers Article Swipe
Sara Stinson
,
Alexey Shadrin
,
Zebunnessa Rahman
,
Linn Rødevand
,
Iris Broce
,
Karin Persson
,
Geir Selbæk
,
Hreinn Stefánsson
,
Jan Haavik
,
Nadine Parker
,
Elise Koch
,
Oleksandr Frei
,
Kevin S. O’Connell
,
Olav B. Smeland
,
Srdjan Djurovic
,
Anders M. Dale
,
Dennis van der Meer
,
Ole A. Andreassen
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.31.25332114
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.31.25332114
Metabolic dysfunction is increasingly implicated in neurodegenerative diseases, yet the genetic architecture linking metabolic markers with Alzheimer’s disease (AD) and Parkinson’s disease (PD) remains unclear. We systematically analysed phenotypic and genetic relationships between 249 circulating metabolites with AD and PD, comparing patterns to body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD) and stroke. Using linkage disequilibrium score regression and bivariate Gaussian mixture modeling, we identified distinct genetic overlap. AD correlated positively with cardiometabolic traits (BMI, r s =0.11; T2D, r s =0.23; CAD, r s =0.22; stroke, r s =0.18), whereas PD showed opposing patterns (AD–PD r s =−0.36). Mendelian randomization identified bi-directional causal effects of lipid measures on AD and divergent effects of glutamine on AD and PD. Conjunctional FDR analyses mapped 1,377 shared genes, implicating lipid metabolism in AD and synaptic processes in PD. These findings disentangle disease-specific pathways and inform therapeutic strategies targeting metabolic health.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.07.31.25332114
- https://www.medrxiv.org/content/medrxiv/early/2025/07/31/2025.07.31.25332114.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 72
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412864544
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412864544Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.07.31.25332114Digital Object Identifier
- Title
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Distinct metabolic signatures of Alzheimer’s and Parkinson’s disease revealed through genetic overlap with metabolic markersWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-07-31Full publication date if available
- Authors
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Sara Stinson, Alexey Shadrin, Zebunnessa Rahman, Linn Rødevand, Iris Broce, Karin Persson, Geir Selbæk, Hreinn Stefánsson, Jan Haavik, Nadine Parker, Elise Koch, Oleksandr Frei, Kevin S. O’Connell, Olav B. Smeland, Srdjan Djurovic, Anders M. Dale, Dennis van der Meer, Ole A. AndreassenList of authors in order
- Landing page
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https://doi.org/10.1101/2025.07.31.25332114Publisher landing page
- PDF URL
-
https://www.medrxiv.org/content/medrxiv/early/2025/07/31/2025.07.31.25332114.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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https://www.medrxiv.org/content/medrxiv/early/2025/07/31/2025.07.31.25332114.full.pdfDirect OA link when available
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Parkinson's disease, Disease, Neuroscience, Genetics, Biology, Medicine, Internal medicineTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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| publication_date | 2025-07-31 |
| publication_year | 2025 |
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