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In particular, the role of the APOE \u03b54 allele as a putative driver of \u03b1-synuclein pathology is a topic of intense debate.<\/jats:p>\n                  <jats:p>Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for dementia with Lewy bodies in patients without APOE \u03b54 (P = 5.65 \u00d7 10\u22128, OR = 3.21, 95% CI = 2.11\u20134.88), but not with dementia with Lewy bodies with APOE \u03b54 (P = 0.034, OR = 1.87, 95%, 95% CI = 1.05\u20133.37). We then divided 495 neuropathologically examined dementia with Lewy bodies cases into three groups based on the extent of concomitant Alzheimer\u2019s disease co-pathology: pure dementia with Lewy bodies (n = 88), dementia with Lewy bodies with intermediate Alzheimer\u2019s disease co-pathology (n = 66) and dementia with Lewy bodies with high Alzheimer\u2019s disease co-pathology (n = 341). In each group, we tested the association of the APOE \u03b54 against the 2928 neurologically healthy controls.<\/jats:p>\n                  <jats:p>Our examination found that APOE \u03b54 was associated with dementia with Lewy bodies + Alzheimer\u2019s disease (P = 1.29 \u00d7 10\u221232, OR = 4.25, 95% CI = 3.35\u20135.39) and dementia with Lewy bodies + intermediate Alzheimer\u2019s disease (P = 0.0011, OR = 2.31, 95% CI = 1.40\u20133.83), but not with pure dementia with Lewy bodies (P = 0.31, OR = 0.75, 95% CI = 0.43\u20131.30).<\/jats:p>\n                  <jats:p>In conclusion, although deep clinical data were not available for these samples, our findings do not support the notion that APOE \u03b54 is an independent driver of \u03b1-synuclein pathology in pure dementia with Lewy bodies, but rather implicate GBA as the main risk gene for the pure dementia with Lewy bodies subgroup.<\/jats:p>","DOI":"10.1093\/brain\/awab402","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T19:59:19Z","timestamp":1634673559000},"page":"1757-1762","source":"Crossref","is-referenced-by-count":69,"title":["Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups"],"prefix":"10.1093","volume":"145","author":[{"given":"Karri","family":"Kaivola","sequence":"first","affiliation":[{"name":"Department of Neurology and Translational Immunology Program, University Hospital and Helsinki University , Helsinki , Finland"},{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zalak","family":"Shah","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke , Bethesda, MD 20892 , 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