MRI-derived atrophy in multiple system atrophy aligns with mitochondrial and glial gene expression patterns
Oligodendroglial pathology is a hallmark of multiple system atrophy (MSA), yet it remains unclear whether MRI-detected atrophy reflects underlying biological mechanisms. This study investigated whether regional atrophy aligns with gene expression and neurotransmitter systems. We recruited 65 MSA patients and derived brain atrophy measures from T1-weighted MRIs. Using postmortem data from the Allen Human Brain Atlas, partial least squares (PLS) regression identified gene expression components associated with brain atrophy. Gene enrichment analyses explored biological processes, and annotation mapping identified neurotransmitter systems matching atrophy patterns. Specificity was tested against 57 patients with Parkinson's disease. Atrophy primarily affected the cerebellar white matter, pons, putamen, olive, and substantia nigra. PLS revealed two latent variables explaining 27.5% of the covariance. Atrophic regions overexpressed genes linked to mitochondrial function and oligodendrocytes, showing patterns distinct from Parkinson's disease. These regions also exhibited lower serotonin and GABA levels, and higher acetylcholine and noradrenaline receptor densities. MRI-derived atrophy in MSA is biologically grounded and may inform future therapeutic studies.
Authors
- Jean‐Christophe Corvol (ORCID: https://orcid.org/0000-0001-7325-0199)
- Justine Y. Hansen (ORCID: https://orcid.org/0000-0003-3142-7480)
- B Degos
- Andrew Vo (ORCID: https://orcid.org/0000-0003-3241-3769)
- D. Grabli
- Aline Delva (ORCID: https://orcid.org/0000-0001-8497-2314)
- Lydia Chougar (ORCID: https://orcid.org/0000-0001-9306-5687)
- Bratislav Mišić (ORCID: https://orcid.org/0000-0003-0307-2862)
- Asa Borzabadi Farahani (ORCID: https://orcid.org/0009-0001-9905-8813)
- C. Payan
- Marie Filiatrault
- Alain Dagher
- Marie Vidailhet
- Charles-Etienne Castonguay
- Christina Tremblay
- Parsa Khalafi
- Shady Rahayel
- Nadya Pyatigorskaya
- Stéphane Lehéricy
- Guy Rouleau
Institutions
- Montreal Neurological Institute and Hospital (CA)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Sorbonne Université (FR)
- Université Sorbonne Paris Nord (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre Interdisciplinaire de Recherche en Biologie (FR)
- Pitié-Salpêtrière Hospital (FR)
- Hôpital Avicenne (FR)
- Hôpital du Sacré-Cœur de Montréal (CA)
- Institut du Cerveau (FR)
- Université de Montréal (CA)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-12-26
- DOI
- https://doi.org/10.1038/s41531-025-01227-1
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Association France Parkinson
- Société Française de Radiologie
- Canada First Research Excellence Fund
- Electricité de France
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé