{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:06:49Z","timestamp":1791860809988,"version":"4.3.4"},"reference-count":228,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000188","name":"Royal Society of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Lewy body\u2010involving diseases (LBD) are commonly associated with Parkinson's disease (PD) featuring voluntary movement inhibition, due to dopaminergic neuron dysfunction in the substantia nigra. PD is clinically tracked through Lewy bodies (LB), composed of insoluble \u03b1\u2010synuclein aggregates sequestered with organelles, particularly inside neurons. However, \u03b1\u2010synuclein pathology also appears in incidental LBD, Parkinson's disease dementia, and dementia with LB (DLB). Incomplete explanations address how these clinical pathologies interrelate, LBD etiology variability, and frequently overlapping \u03b1\u2010synuclein and Alzheimer's disease (AD) pathologies. We hypothesize that (1) chronic environmental insult exposure and (2) senescence(\u2010like) neuron accumulation contribute toward initiating and sustaining LBD; individual cell vulnerability determines either cell reactivity, death, or senescence in response to environmental insults. We predicate that parkinsonian and other neurodegenerative symptoms over LBD progression involve (3) co\u2010occurring AD pathologies, wherein dementia symptomology develops when synergistic glial senescence, tau hyperphosphorylation, and possible \u03b1\u2010synuclein aggregation reach into regions involved in AD progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Senescence burden is predicted to explain \u03b1\u2010synucleinopathy progression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Senescence and cell death are hypothesized to occur in \u03b1\u2010synucleinopathies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sub\u2010apoptotic stress is proposed to induce senescence in \u03b1\u2010synucleinopathies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neuronal senescence likely first spreads \u03b1\u2010synucleinopathies to new regions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Glial senescence likely underlies Parkinson's disease and Alzheimer's disease overlap.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70363","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T23:53:22Z","timestamp":1750204402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A hypothesis explaining Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies overlap"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-2073","authenticated-orcid":false,"given":"Victor Z.","family":"Lau","sequence":"first","affiliation":[{"name":"Division of Medical Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Institute on Aging and Lifelong Health (IALH), University of Victoria  Victoria British Columbia Canada"},{"name":"Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria  Victoria British Columbia Canada"},{"name":"Vulnerable Brain Laboratory Department of Anatomy and Cell Biology The Schulich School of Medicine &amp; Dentistry, The University of Western Ontario  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6786-3658","authenticated-orcid":false,"given":"Ifeoluwa O.","family":"Awogbindin","sequence":"additional","affiliation":[{"name":"Division of Medical Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Institute on Aging and Lifelong Health (IALH), University of Victoria  Victoria British Columbia Canada"},{"name":"Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-6857","authenticated-orcid":false,"given":"Dan","family":"Frenkel","sequence":"additional","affiliation":[{"name":"Department of Neurobiology The School of Neurobiology, Biochemistry, and Biophysics, George S. 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