Regional gene expression and brain atrophy in dementia with Lewy bodies: an imaging transcriptomics study

Regional brain atrophy has been observed in dementia with Lewy bodies (DLB), yet determinants of regional vulnerability remain unclear. Using imaging transcriptomics, we examined whether normative gene expression patterns relate to regional atrophy in DLB. We included 164 DLB patients (49 women) and 164 age- and sex-matched healthy controls from three European centres and the Mayo Clinic, USA. Volumetric atrophy was quantified from T1-weighted MRI across 58 left-hemispheric regions using w-scores. Normative expression of twelve genes implicated in alpha-synuclein, beta-amyloid, and tau pathology was extracted from the Allen Human Brain Atlas. DLB patients showed diffuse atrophy across most regions. In the full cohort, normative expression of MAPT, PINK1, and PSEN2 predicted regional atrophy after correction for spatial autocorrelation, although none survived multiple-testing correction. In the Mayo Clinic sub-cohort, expression of APP, BIN1, GBA, MAPT, PINK1, SNCA, and TMEM175 significantly predicted atrophy and survived multiple-testing correction. Random forest models did not outperform spatial null models in the full cohort, but PARK7, PINK1, and PSEN2 consistently emerged as important predictors. A significant global model was observed in the Mayo Clinic sub-cohort, driven by GBA, LRP1, and PINK1. These findings suggest that normative gene expression partially contributes to regional brain atrophy in DLB.

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Journal
npj Parkinson s Disease
Published
2026-04-16
DOI
https://doi.org/10.1038/s41531-026-01355-2
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Regional gene expression and brain atrophy in dementia with Lewy bodies: an imaging transcriptomics study

Scott A. Przybelski, Ketil Oppedal, Annegret Habich, Janna M. Baumann et al.
npj Parkinson s Disease
Dementia and Cognitive Impairment Research
article

Regional gene expression and brain atrophy in dementia with Lewy bodies: an imaging transcriptomics study

Scott A. Przybelski, Ketil Oppedal, Annegret Habich, Janna M. Baumann, Thomas Dierks, Afina W. Lemstra, Frédéric Blanc, Daniel Ferreira, Jakub Hort, Bradley F. Boeve, Dag Aarsland, Kejal Kantarci, Eric Westman, Christopher G. Schwarz, Anna Inguanzo, Laura E. Jonkman
article en

Abstract

Regional brain atrophy has been observed in dementia with Lewy bodies (DLB), yet determinants of regional vulnerability remain unclear. Using imaging transcriptomics, we examined whether normative gene expression patterns relate to regional atrophy in DLB. We included 164 DLB patients (49 women) and 164 age- and sex-matched healthy controls from three European centres and the Mayo Clinic, USA. Volumetric atrophy was quantified from T1-weighted MRI across 58 left-hemispheric regions using w-scores. Normative expression of twelve genes implicated in alpha-synuclein, beta-amyloid, and tau pathology was extracted from the Allen Human Brain Atlas. DLB patients showed diffuse atrophy across most regions. In the full cohort, normative expression of MAPT, PINK1, and PSEN2 predicted regional atrophy after correction for spatial autocorrelation, although none survived multiple-testing correction. In the Mayo Clinic sub-cohort, expression of APP, BIN1, GBA, MAPT, PINK1, SNCA, and TMEM175 significantly predicted atrophy and survived multiple-testing correction. Random forest models did not outperform spatial null models in the full cohort, but PARK7, PINK1, and PSEN2 consistently emerged as important predictors. A significant global model was observed in the Mayo Clinic sub-cohort, driven by GBA, LRP1, and PINK1. These findings suggest that normative gene expression partially contributes to regional brain atrophy in DLB.

npj Parkinson s DiseaseVol. 12(1)
University of Bern (CH), Centre National de la Recherche Scientifique (FR), Bern University of Applied Sciences (CH), King's College London (GB), Charles University (CZ), Stavanger University Hospital (NO), University Hospital of Bern (CH), Karolinska Institutet (SE), Universidad Fernando Pessoa Canarias (ES), Amsterdam Neuroscience (NL), Mayo Clinic in Arizona (US), Hôpitaux Universitaires de Strasbourg (FR), Mayo Clinic in Florida (US), Amsterdam University Medical Centers (NL), Université de Strasbourg (FR), Vrije Universiteit Amsterdam (NL), University of Stavanger (NO)
Eli Lilly and Company, AstraZeneca, Biogen, Åke Wiberg Stiftelse, Little Family Foundation, Stiftelsen för Gamla Tjänarinnor, Ministerstvo Školství, Mládeže a Tělovýchovy, Université de Strasbourg, Eisai, Hjärnfonden, Karolinska Institutet, Vetenskapsrådet, Alzheimerfonden, H. Lundbeck A/S, Demensfonden, National Institutes of Health, Parkinsonfonden, Avid Radiopharmaceuticals, Tau Consortium, Center for Innovative Medicine
Openalex Percentile: Top 20%
Dementia and Cognitive Impairment Research
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