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We show that in PD brain tissue, the levels of LRRK2 are positively related to the increase in \u03b1-synuclein phosphorylation and aggregation in affected brain regions (amygdala and anterior cingulate cortex), but not in the unaffected visual cortex. In disease-affected regions, we show co-localization of these two proteins in neurons and Lewy body inclusions. Further, in vitro experiments show a molecular interaction between \u03b1-synuclein and LRRK2 under endogenous and over-expression conditions. In a cell culture model of \u03b1-synuclein inclusion formation, LRRK2 co-localizes with the \u03b1-synuclein inclusions, and knocking down LRRK2 increases the number of smaller inclusions. In addition to providing strong evidence for an interaction between LRRK2 and \u03b1-synuclein, our results shed light on the complex relationship between these two proteins in the brains of patients with PD and the underlying molecular mechanisms of the disease.<\/jats:p>","DOI":"10.1007\/s00109-012-0984-y","type":"journal-article","created":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T14:13:06Z","timestamp":1353939186000},"page":"513-522","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["LRRK2 interactions with \u03b1-synuclein in Parkinson\u2019s disease brains and in cell models"],"prefix":"10.1007","volume":"91","author":[{"given":"Patr\u00edcia Silva","family":"Guerreiro","sequence":"first","affiliation":[]},{"given":"Yue","family":"Huang","sequence":"additional","affiliation":[]},{"given":"Amanda","family":"Gysbers","sequence":"additional","affiliation":[]},{"given":"Danni","family":"Cheng","sequence":"additional","affiliation":[]},{"given":"Wei Ping","family":"Gai","sequence":"additional","affiliation":[]},{"given":"Tiago Fleming","family":"Outeiro","sequence":"additional","affiliation":[]},{"given":"Glenda Margaret","family":"Halliday","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,11,27]]},"reference":[{"key":"984_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1001\/archneur.56.1.33","volume":"56","author":"DJ Gelb","year":"1999","unstructured":"Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. 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