{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T16:12:07Z","timestamp":1781194327735,"version":"3.54.1"},"reference-count":45,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,8,31]]},"abstract":"<jats:p>Background: Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity. Objective: We tested if genetic variants in part explain the heterogeneity in DLB. Methods: We tested the effects of variants previously associated with DLB (near APOE, GBA, and SNCA) and polygenic risk scores for Alzheimer\u2019s disease (AD-PRS) and Parkinson\u2019s disease (PD-PRS). We studied 190 probable DLB patients from the Alzheimer\u2019s dementia cohort and compared them to 2,552 control subjects. The p-tau\/A\u03b21\u201342 ratio in cerebrospinal fluid was used as in vivo proxy to separate DLB cases into DLB with concomitant AD pathology (DLB-AD) or DLB without AD (DLB-pure). We studied the clinical measures age, Mini-Mental State Examination (MMSE), and the presence of core symptoms at diagnosis and disease duration. Results: We found that all studied genetic factors significantly associated with DLB risk (all-DLB). Second, we stratified the DLB patients by the presence of concomitant AD pathology and found that APOE \u025b4 and the AD-PRS associated specifically with DLB-AD, but less with DLB-pure. In addition, the GBA p.E365K variant showed strong associated with DLB-pure and less with DLB-AD. Last, we studied the clinical measures and found that APOE \u025b4 associated with reduced MMSE, higher odds to have fluctuations and a shorter disease duration. In addition, the GBA p.E365K variant reduced the age at onset by 5.7 years, but the other variants and the PRS did not associate with clinical features. Conclusion: These finding increase our understanding of the pathological and clinical heterogeneity in DLB.<\/jats:p>","DOI":"10.3233\/jad-210365","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T11:10:04Z","timestamp":1627038604000},"page":"269-279","source":"Crossref","is-referenced-by-count":24,"title":["Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies"],"prefix":"10.1177","volume":"83","author":[{"given":"Sven J.","family":"van der Lee","sequence":"first","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Section Genomics of Neurdegenerative Diseases and Aging, Department of Human Genetics Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"van Steenoven","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"van de Beek","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f2","family":"Tesi","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Section Genomics of Neurdegenerative Diseases and Aging, Department of Human Genetics Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Pattern Recognition & Bioinformatics, Delft University of Technology, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris E.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije University, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasja M.","family":"van Schoor","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel J.T.","family":"Reinders","sequence":"additional","affiliation":[{"name":"Pattern Recognition & Bioinformatics, Delft University of Technology, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Huisman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands"},{"name":"Department of Sociology, VU University, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E.","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henne","family":"Holstege","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Section Genomics of Neurdegenerative Diseases and Aging, Department of Human Genetics Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiesje M.","family":"van der Flier","sequence":"additional","affiliation":[{"name":"Alzheimer Center Amsterdam, Department of Neurology, 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