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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\n                    <jats:italic>w<\/jats:italic>\n                    -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\n                    <jats:italic>MAPT<\/jats:italic>\n                    ,\n                    <jats:italic>PINK1<\/jats:italic>\n                    , and\n                    <jats:italic>PSEN2<\/jats:italic>\n                    predicted regional atrophy after correction for spatial autocorrelation, although none survived multiple-testing correction. In the Mayo Clinic sub-cohort, expression of\n                    <jats:italic>APP<\/jats:italic>\n                    ,\n                    <jats:italic>BIN1<\/jats:italic>\n                    ,\n                    <jats:italic>GBA<\/jats:italic>\n                    ,\n                    <jats:italic>MAPT<\/jats:italic>\n                    ,\n                    <jats:italic>PINK1<\/jats:italic>\n                    ,\n                    <jats:italic>SNCA<\/jats:italic>\n                    , and\n                    <jats:italic>TMEM175<\/jats:italic>\n                    significantly predicted atrophy and survived multiple-testing correction. Random forest models did not outperform spatial null models in the full cohort, but\n                    <jats:italic>PARK7<\/jats:italic>\n                    ,\n                    <jats:italic>PINK1<\/jats:italic>\n                    , and\n                    <jats:italic>PSEN2<\/jats:italic>\n                    consistently emerged as important predictors. A significant global model was observed in the Mayo Clinic sub-cohort, driven by\n                    <jats:italic>GBA<\/jats:italic>\n                    ,\n                    <jats:italic>LRP1<\/jats:italic>\n                    , and\n                    <jats:italic>PINK1<\/jats:italic>\n                    . These findings suggest that normative gene expression partially contributes to regional brain atrophy in DLB.\n                  <\/jats:p>","DOI":"10.1038\/s41531-026-01355-2","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:59:19Z","timestamp":1776333559000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regional gene expression and brain atrophy in dementia with Lewy bodies: an imaging transcriptomics study"],"prefix":"10.1038","volume":"12","author":[{"given":"Annegret","family":"Habich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna M.","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Przybelski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Inguanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketil","family":"Oppedal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Blanc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afina W.","family":"Lemstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Hort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley F.","family":"Boeve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Westman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Dierks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejal","family":"Kantarci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Jonkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"1355_CR1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.neuroimage.2004.04.026","volume":"23","author":"M Ballmaier","year":"2004","unstructured":"Ballmaier, M. et al. 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FB has served as national coordinator and principal investigator for clinical trials sponsored by Biogen, Roche, Axovant and Eisai. BFB has served as an investigator for clinical trials sponsored by Biogen and Alector. He receives royalties from the publication of a book entitled Behavioural Neurology of Dementia (Cambridge Medicine, 2017), serves on the Scientific Advisory Board of the Tau Consortium, and receives research support from NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Ted Turner and Family Foundation LBD Functional Genomics Program. DA has received research support and\/or honoraria from AstraZeneca, H. Lundbeck, Novartis Pharmaceuticals and GE Health, and served as paid consultant for H. Lundbeck, Eisai and Evonik. KK serves on the data safety monitoring board for Takeda Global Research and Development Center, Inc., receives research support from Avid Radiopharmaceuticals and Eli Lilly, and receives funding from NIH and Alzheimer\u2019s Drug Discovery Foundation. DF consults for BioArctic and has received honoraria from Esteve.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"96"}}