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It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid \u03b2 (A\u03b2) and tau accumulation, occur in some LBD cases. We sought to quantify \u03b1\u2010syn, A\u03b2, and tau accumulation in neocortical, limbic, and basal ganglia regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble \u03b1\u2010syn, A\u03b2, and tau with recently developed sandwich ELISAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected a wide range of insoluble \u03b1\u2010syn accumulation in LBD cases. The majority had substantial \u03b1\u2010syn accumulation in most regions, and dementia severity correlated with neocortical \u03b1\u2010syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial A\u03b2 accumulation, although the mean A\u03b2 level in LBD was lower than in AD. The presence of A\u03b2 was associated with greater \u03b1\u2010syn accumulation. Tau accumulation accompanied A\u03b2 in only one LBD case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>LBD is associated with insoluble \u03b1\u2010syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between A\u03b2 and \u03b1\u2010syn accumulation suggests a pathophysiologic relationship between these two processes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51482","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T09:58:25Z","timestamp":1642759105000},"page":"106-121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Quantifying regional \u03b1 \u2010synuclein, amyloid \u03b2, and tau accumulation in lewy body dementia"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1227-5891","authenticated-orcid":false,"given":"Rebecca L.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University School of Medicine St. Louis MO"},{"name":"Hope Center for Neurological Disorders Washington University School of Medicine St. Louis 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