{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:33:35Z","timestamp":1791387215228,"version":"4.3.3"},"reference-count":68,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T00:00:00Z","timestamp":1703894400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2024,1,23]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Parkinson\u2019s disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein ( \u03b1-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops \u03b1-syn aggregates in DLB and PDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To investigate the long-term behavioral and cognitive consequences of \u03b1-syn pathology in the cortex and characterize pathological spread of \u03b1-syn.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We injected human \u03b1-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological \u03b1-syn in cortical, subcortical, and brainstem regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We report that PFC PFFs: 1) induced \u03b1-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This model of cortical-dominant pathology aids in our understanding of how local \u03b1-syn aggregation might impact some symptoms in PDD and DLB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jpd-230129","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T11:12:23Z","timestamp":1704193943000},"page":"81-94","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures"],"prefix":"10.1177","volume":"14","author":[{"given":"Matthew A.","family":"Weber","sequence":"first","affiliation":[{"name":"Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Kerr","sequence":"additional","affiliation":[{"name":"Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramasamy","family":"Thangavel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie M.","family":"Conlon","sequence":"additional","affiliation":[{"name":"Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena B.","family":"Gumusoglu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA"},{"name":"Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Neurology, Carver College 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