Influence of alpha‐synuclein on glucose metabolism in Alzheimer's disease continuum: Analyses of α‐synuclein seed amplification assay and FDG‐PET
α-synuclein seed amplification positivity (SAA+) was associated with hypometabolism in cognitively impaired individuals. Hypometabolism mediated the influence of α-synuclein on disease severity. Occipital hypometabolism in SAA+ was independent of cerebrospinal fluid levels of Alzheimer's disease pathology. These findings can optimize future clinical trials targeting α-synuclein pathology.
Authors
- Val J. Lowe (ORCID: https://orcid.org/0000-0002-5612-1667)
- Clifford R. Jack (ORCID: https://orcid.org/0000-0001-7916-622X)
- John T. O’Brien (ORCID: https://orcid.org/0000-0002-0837-5080)
- Scott A. Przybelski (ORCID: https://orcid.org/0009-0009-3437-3773)
- Ronald Carl Petersen (ORCID: https://orcid.org/0000-0002-8178-6601)
- Matthew L. Senjem (ORCID: https://orcid.org/0000-0001-9308-9275)
- Elijah Mak (ORCID: https://orcid.org/0000-0002-6437-8024)
- Christopher G. Schwarz (ORCID: https://orcid.org/0000-0002-1466-8357)
- Bradley F. Boeve (ORCID: https://orcid.org/0000-0002-4153-8187)
- Kejal Kantarci (ORCID: https://orcid.org/0000-0002-8001-2081)
- Angela J. Fought (ORCID: https://orcid.org/0000-0002-7486-8596)
- Heather J. Wiste (ORCID: https://orcid.org/0009-0002-8833-2693)
Institutions
- Mayo Clinic (US)
- University of Cambridge (GB)
- WinnMed (US)
- Mayo Clinic in Florida (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1002/alz.14571
- Citations
- 4
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.56
Funders
- U.S. Department of Defense
- Alzheimer's Association
- Bristol-Myers Squibb
- Alzheimer's Drug Discovery Foundation
- Eli Lilly and Company
- Pfizer
- Biogen
- University of Southern California
- Mayo Foundation for Medical Education and Research
- Meso Scale Diagnostics
- Alzheimer's Disease Neuroimaging Initiative
- BioClinica
- Novartis Pharmaceuticals Corporation
- Northern California Institute for Research and Education
- Little Family Foundation
- Elsie and Marvin Dekelboum Family Foundation
- Alzheimer's Society
- National Institute for Health and Care Research
- Eisai
- Servier
- H. Lundbeck A/S
- IXICO
- National Institutes of Health
- Genentech
- Canadian Institutes of Health Research
- NIHR Cambridge Biomedical Research Centre