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This review explores the clinical and neuropathological heterogeneity of DLB, which complicates its early diagnosis, prognosis, and treatment. The staging of Lewy body (LB) pathology varies, with both brain-first and body-first hypotheses suggesting different origins and pathways for disease progression. Co-pathologies, such as amyloid-\u03b2 plaques, tau tangles, and cerebrovascular changes, further influence the clinical presentation and rate of disease progression in DLB patients, contributing to significant variability. In this review, the role of genetic factors, particularly APOE \u03b54 and GBA mutations, in shaping DLB\u2019s clinical and pathological diversity is also emphasized. Heterogeneous manifestations, including REM sleep behavior disorder (RBD), mild cognitive impairment, and psychiatric-onset DLB, highlight the need for improved biomarkers to guide early diagnosis. Neuroimaging techniques such as [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG PET and [\n                      <jats:sup>123<\/jats:sup>\n                      I]FP-CIT SPECT help distinguish DLB from other dementias, like Alzheimer\u2019s disease (AD), though challenges remain in identifying co-pathologies with precision.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, the paper explores the complexity of DLB\u2019s heterogeneous nature, advocating for deeper exploration of its diverse pathological pathways, genetic predispositions, and clinical profiles to improve diagnosis and treatment outcomes. Understanding this heterogeneity is crucial for the development of personalized therapeutic strategies and effective management of the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10072-025-08725-3","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T13:24:45Z","timestamp":1766496285000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Heterogeneity of dementia with Lewy bodies: Insights from clinical presentations, neuropathology, and biomarkers"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9983-7940","authenticated-orcid":false,"given":"Beatrice","family":"Orso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Bollack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulfiqar H.","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Morbelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gill","family":"Farrar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"8725_CR1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","volume":"89","author":"IG McKeith","year":"2017","unstructured":"McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor J-P, Weintraub D et al (2017) Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. 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As this is a literature-based review, no ethical approval was required.BO has received research support from GE Healthcare (paid to institution). ZHS, GF and AB are employees of GE HealthCare. SM: speaker Honoraria from G.E. Healthcare, Life Molecular Imaging and Eli Lilly. MP: received research support from Novartis and Nutricia, received fees from Novartis, Merck and Biogen.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"BO has received research support from GE Healthcare (paid to institution). ZHS, GF and AB are employees of GE HealthCare. SM: speaker Honoraria from G.E. Healthcare, Life Molecular Imaging and Eli Lilly. MP: received research support from Novartis and Nutricia, received fees from Novartis, Merck and Biogen.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"31"}}