{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:43:14Z","timestamp":1790347394071,"version":"4.1.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>\n              <jats:italic>ATP13A2<\/jats:italic> (<jats:italic>PARK9<\/jats:italic>) loss of function mutations are a genetic cause of an early-onset form of Parkinson\u2019s disease (PD), with <jats:italic>in vitro<\/jats:italic> studies showing that ATP13A2 deficits lead to lysosomal and mitochondrial dysfunction and \u03b1-synuclein accumulation, while elevated ATP13A2 expression reduces \u03b1-synuclein toxicity. The three human brain tissue studies assessing changes in ATP13A2 expression in PD produced divergent results; mRNA is increased while protein levels were observed to be either increased or decreased. This apparent conflict in protein levels might have arisen from examining Lewy body disease cases with coexisting Alzheimer-type pathologies.<\/jats:p>\n            <jats:p>To assess whether ATP13A2 levels in Lewy body disease are modified by Alzheimer-type \u03b2-amyloid deposition, we evaluated cases of pure PD and pure dementia with Lewy bodies (DLB) for changes in ATP13A2, \u03b1-synuclein and \u03b2-amyloid protein levels in cortical regions with and without Lewy bodies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In all Lewy body disease cases, we identified decreased ATP13A2 protein levels that correlated with increases in both \u03b1-synuclein and \u03b2-amyloid. Partial colocalization was observed between ATP13A2 and \u03b1-synuclein in Lewy bodies, whereas ATP13A2 did not colocalize with pathological \u03b2-amyloid deposition.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our data show that patients with Lewy body diseases have an overall deficit in ATP13A2 protein levels, with the remaining protein being more insoluble and partially redistributing towards Lewy bodies. This supports the concept that increasing ATP13A2 levels may offer potential therapeutic benefits to patients with Lewy body diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/2051-5960-1-11","type":"journal-article","created":{"date-parts":[[2013,5,9]],"date-time":"2013-05-09T08:14:19Z","timestamp":1368087259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["ATP13A2 (PARK9) protein levels are reduced in brain tissue of cases with Lewy bodies"],"prefix":"10.1186","volume":"1","author":[{"given":"Karen E","family":"Murphy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Cottle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M","family":"Gysbers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony A","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda M","family":"Halliday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,5,9]]},"reference":[{"key":"6_CR1","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1038\/ng1884","volume":"38","author":"A Ramirez","year":"2006","unstructured":"Ramirez A, Heimbach A, Grundemann J, Stiller B, Hampshire D, Cid LP, Goebel I, Mubaidin AF, Wriekat AL, Roeper J, Al-Din A, Hillmer AM, Karsak M, Liss B, Woods CG, Behrens MI, Kubisch C: Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 2006, 38: 1184\u20131191. 10.1038\/ng1884","journal-title":"Nat Genet"},{"key":"6_CR2","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/ng.300","volume":"41","author":"AD Gitler","year":"2009","unstructured":"Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S: Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nat Genet 2009, 41: 308\u2013315. 10.1038\/ng.300","journal-title":"Nat Genet"},{"key":"6_CR3","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1002\/humu.21527","volume":"32","author":"JS Park","year":"2011","unstructured":"Park JS, Mehta P, Cooper AA, Veivers D, Heimbach A, Stiller B, Kubisch C, Fung VS, Krainc D, Mackay-Sim A, Sue CM: Pathogenic effects of novel mutations in the P-type ATPase ATP13A2 (PARK9) causing Kufor-Rakeb syndrome, a form of early-onset parkinsonism. Hum Mutat 2011, 32: 956\u2013964. 10.1002\/humu.21527","journal-title":"Hum Mutat"},{"key":"6_CR4","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1093\/hmg\/ddr606","volume":"21","author":"D Ramonet","year":"2012","unstructured":"Ramonet D, Podhajska A, Stafa K, Sonnay S, Trancikova A, Tsika E, Pletnikova O, Troncoso JC, Glauser L, Moore DJ: PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and regulates cation homeostasis and neuronal integrity. Hum Mol Genet 2012, 21: 1725\u20131743. 10.1093\/hmg\/ddr606","journal-title":"Hum Mol Genet"},{"key":"6_CR5","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.4161\/auto.21011","volume":"8","author":"B Dehay","year":"2012","unstructured":"Dehay B, Martinez-Vicente M, Ramirez A, Perier C, Klein C, Vila M, Bezard E: Lysosomal dysfunction in Parkinson disease: ATP13A2 gets into the groove. Autophagy 2012, 8: 1389\u20131391.","journal-title":"Autophagy"},{"key":"6_CR6","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.nbd.2011.12.015","volume":"45","author":"AM Gusdon","year":"2011","unstructured":"Gusdon AM, Zhu J, Van Houten B, Chu CT: ATP13A2 regulates mitochondrial bioenergetics through macroautophagy. Neurobiol Dis 2011, 45: 962\u2013972.","journal-title":"Neurobiol Dis"},{"key":"6_CR7","doi-asserted-by":"publisher","first-page":"987","DOI":"10.4161\/auto.20256","volume":"8","author":"M Usenovic","year":"2012","unstructured":"Usenovic M, Krainc D: Lysosomal dysfunction in neurodegeneration: the role of ATP13A2\/PARK9. Autophagy 2012, 8: 987\u2013988.","journal-title":"Autophagy"},{"key":"6_CR8","doi-asserted-by":"publisher","first-page":"9611","DOI":"10.1073\/pnas.1112368109","volume":"109","author":"B Dehay","year":"2012","unstructured":"Dehay B, Ramirez A, Martinez-Vicente M, Perier C, Canron MH, Doudnikoff E, Vital A, Vila M, Klein C, Bezard E: Loss of P-type ATPase ATP13A2\/PARK9 function induces general lysosomal deficiency and leads to Parkinson disease neurodegeneration. Proc Natl Acad Sci U S A 2012, 109: 9611\u20139616. 10.1073\/pnas.1112368109","journal-title":"Proc Natl Acad Sci U S A"},{"key":"6_CR9","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/S0197-4580(97)00057-2","volume":"18","author":"The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer\u2019s Disease","year":"1997","unstructured":"The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer\u2019s Disease: Consensus recommendations for the postmortem diagnosis of Alzheimer\u2019s disease. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer\u2019s Disease. Neurobiol Aging 1997, 18: S1-S2.","journal-title":"Neurobiol Aging"},{"key":"6_CR10","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00401-011-0815-1","volume":"121","author":"J Zhou","year":"2011","unstructured":"Zhou J, Broe M, Huang Y, Anderson JP, Gai WP, Milward EA, Porritt M, Howells D, Hughes AJ, Wang X, Halliday GM: Changes in the solubility and phosphorylation of alpha-synuclein over the course of Parkinson\u2019s disease. Acta Neuropathol 2011, 121: 695\u2013704. 10.1007\/s00401-011-0815-1","journal-title":"Acta Neuropathol"},{"key":"6_CR11","doi-asserted-by":"publisher","first-page":"4240","DOI":"10.1523\/JNEUROSCI.5575-11.2012","volume":"32","author":"M Usenovic","year":"2012","unstructured":"Usenovic M, Tresse E, Mazzulli JR, Taylor JP, Krainc D: Deficiency of ATP13A2 Leads to Lysosomal Dysfunction, alpha-Synuclein Accumulation, and Neurotoxicity. J Neurosci 2012, 32: 4240\u20134246. 10.1523\/JNEUROSCI.5575-11.2012","journal-title":"J Neurosci"},{"key":"6_CR12","doi-asserted-by":"publisher","first-page":"e34178","DOI":"10.1371\/journal.pone.0034178","volume":"7","author":"A Chesi","year":"2012","unstructured":"Chesi A, Kilaru A, Fang X, Cooper AA, Gitler AD: The Role of the Parkinson\u2019s Disease Gene PARK9 in Essential Cellular Pathways and the Manganese Homeostasis Network in Yeast. PLoS One 2012, 7: e34178. 10.1371\/journal.pone.0034178","journal-title":"PLoS One"},{"key":"6_CR13","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1093\/hmg\/dds206","volume":"21","author":"M Usenovic","year":"2012","unstructured":"Usenovic M, Knight AL, Ray A, Wong V, Brown KR, Caldwell GA, Caldwell KA, Stagljar I, Krainc D: Identification of novel ATP13A2 interactors and their role in alpha-synuclein misfolding and toxicity. Hum Mol Genet 2012, 21: 3785\u20133794. 10.1093\/hmg\/dds206","journal-title":"Hum Mol Genet"},{"key":"6_CR14","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","volume":"24","author":"H Braak","year":"2003","unstructured":"Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E: Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiol Aging 2003, 24: 197\u2013211. 10.1016\/S0197-4580(02)00065-9","journal-title":"Neurobiol Aging"},{"key":"6_CR15","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/S1474-4422(09)70238-8","volume":"8","author":"DW Dickson","year":"2009","unstructured":"Dickson DW, Braak H, Duda JE, Duyckaerts C, Gasser T, Halliday GM, Hardy J, Leverenz JB, Del Tredici K, Wszolek ZK, Litvan I: Neuropathological assessment of Parkinson\u2019s disease: refining the diagnostic criteria. Lancet Neurol 2009, 8: 1150\u20131157. 10.1016\/S1474-4422(09)70238-8","journal-title":"Lancet Neurol"},{"issue":"Suppl 1","key":"6_CR16","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1017\/S1041610297004870","volume":"9","author":"JC Morris","year":"1997","unstructured":"Morris JC: Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psychogeriatr 1997,9(Suppl 1):173\u2013176.","journal-title":"Int Psychogeriatr"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/2051-5960-1-11.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T23:44:24Z","timestamp":1630539864000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/2051-5960-1-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,9]]},"references-count":16,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["6"],"URL":"https:\/\/doi.org\/10.1186\/2051-5960-1-11","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,9]]},"assertion":[{"value":"25 March 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"11"}}