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Postmortem studies of PD have suggested that initial alpha\u2010synuclein (\u03b1\u2010Syn) pathology develops independently in the olfactory bulb and lower brainstem, spreading from there stereotypically. However, it remains unclear how these two pathological pathways contribute to the clinicopathological progression of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to examine the clinicopathological contribution of \u03b1\u2010Syn spread from the olfactory bulb.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted pathological and behavioral analyses of human \u03b1\u2010Syn bacterial artificial chromosome transgenic mice injected with \u03b1\u2010Syn preformed fibrils into the bilateral olfactory bulb up to 10\u2009months postinjection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\u03b1\u2010Syn preformed fibril injections induced more widespread \u03b1\u2010Syn pathology in the transgenic mice than that in wild\u2010type mice. Severe \u03b1\u2010Syn pathology in the transgenic mice injected with \u03b1\u2010Syn preformed fibrils was initially observed along the olfactory pathway and later in the brain regions that are included in the limbic system and have connections with it. The \u03b1\u2010Syn pathology was accompanied by regional atrophy, neuron loss, reactive astrogliosis, and microglial activation, which were remarkable in the hippocampus. Behavioral analyses revealed hyposmia, followed by anxiety\u2010like behavior and memory impairment, but not motor dysfunction, depression\u2010like behavior, or circadian rhythm disturbance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data suggest that \u03b1\u2010Syn spread from the olfactory bulb mainly affects the olfactory pathway and limbic system as well as its related regions, leading to the development of hyposmia, anxiety, and memory loss in PD. \u00a9 2021 International Parkinson and Movement Disorder Society<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.28512","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T13:21:22Z","timestamp":1612790482000},"page":"2036-2047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["<scp>\u03b1<\/scp>\n                    \u2010Synuclein Spread from Olfactory Bulb Causes Hyposmia, Anxiety, and Memory Loss in\n                    <scp>\n                      BAC\u2010\n                      <i>SNCA<\/i>\n                    <\/scp>\n                    Mice"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6251-0810","authenticated-orcid":false,"given":"Norihito","family":"Uemura","sequence":"first","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine  Kyoto Japan"},{"name":"Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research University of Pennsylvania School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-7923","authenticated-orcid":false,"given":"Jun","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto 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