{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:43:43Z","timestamp":1792532623569,"version":"4.5.0"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["F30AG067673"],"award-info":[{"award-number":["F30AG067673"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pathological tau inclusions are neuropathologic hallmarks of many neurodegenerative diseases. We generated and characterized a transgenic mouse model expressing pathogenic human tau with S320F and P301S aggregating mutations (SPAM) at transgene levels below endogenous mouse tau protein levels. This mouse model develops a predictable temporal progression of tau pathology in the brain with biochemical and ultrastructural properties akin to authentic tau inclusions. Surprisingly, pathogenic human tau extensively recruited endogenous mouse tau into insoluble aggregates. Despite the early onset and rapid progressive nature of tau pathology, major neuroinflammatory and transcriptional changes were only detectable at later time points. Moreover, tau SPAM mice are the first model to develop loss of enteric neurons due to tau accumulation resulting in a lethal phenotype. With moderate transgene expression, rapidly progressing tau pathology, and a highly predictable lethal phenotype, the tau SPAM model reveals new associations of tau neurotoxicity in the brain and intestinal tract.<\/jats:p>","DOI":"10.1038\/s42003-022-03373-1","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T06:33:06Z","timestamp":1652337186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Pathogenic tau recruits wild-type tau into brain inclusions and induces gut degeneration in transgenic SPAM mice"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8415-8256","authenticated-orcid":false,"given":"Yuxing","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Prokop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brach M.","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly-Marie M.","family":"Gorion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7969-5084","authenticated-orcid":false,"given":"Cara L.","family":"Croft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5515-6115","authenticated-orcid":false,"given":"Lith","family":"Nasif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara J.","family":"Riffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa N.","family":"Manaois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin H.","family":"Strang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5880-8470","authenticated-orcid":false,"given":"Stephan S.","family":"Quintin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giavanna","family":"Paterno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-4708","authenticated-orcid":false,"given":"Mal\u00fa G\u00e1mez","family":"Tansey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Borchelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd E.","family":"Golde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2992-4234","authenticated-orcid":false,"given":"Benoit I.","family":"Giasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"3373_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.31887\/DCNS.2009.11.2\/cqiu","volume":"11","author":"C Qiu","year":"2009","unstructured":"Qiu, C., Kivipelto, M. & von Strauss, E. Epidemiology of Alzheimer\u2019s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin. Neurosci. 11, 111\u2013128 (2009).","journal-title":"Dialogues Clin. Neurosci."},{"key":"3373_CR2","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack","year":"2018","unstructured":"Jack, C. R. et al. NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 14, 535\u2013562 (2018).","journal-title":"Alzheimers Dement."},{"key":"3373_CR3","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/31508","volume":"393","author":"M Hutton","year":"1998","unstructured":"Hutton, M. et al. Association of missense and 5\u2032-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702\u2013705 (1998).","journal-title":"Nature"},{"key":"3373_CR4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrn.2015.1","volume":"17","author":"Y Wang","year":"2016","unstructured":"Wang, Y. & Mandelkow, E. Tau in physiology and pathology. Nat. Rev. Neurosci. 17, 5\u201321 (2016).","journal-title":"Nat. Rev. Neurosci."},{"key":"3373_CR5","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3389\/fneur.2012.00052","volume":"3","author":"D Galimberti","year":"2012","unstructured":"Galimberti, D. & Scarpini, E. Genetics of frontotemporal lobar degeneration. Front. Neurol. 3, 52 (2012).","journal-title":"Front. Neurol."},{"key":"3373_CR6","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fnins.2018.00025","volume":"12","author":"F Kametani","year":"2018","unstructured":"Kametani, F. & Hasegawa, M. Reconsideration of Amyloid hypothesis and Tau hypothesis in Alzheimer\u2019s disease. Front. Neurosci. 12, 25 (2018).","journal-title":"Front. Neurosci."},{"key":"3373_CR7","doi-asserted-by":"crossref","unstructured":"Myers, A. & McGonigle, P. Overview of transgenic mouse models for Alzheimer\u2019s disease. Curr. Protoc. Neurosci. 89, e81 (2019).","DOI":"10.1002\/cpns.81"},{"key":"3373_CR8","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1101\/sqb.2018.83.037531","volume":"83","author":"Z Joel","year":"2018","unstructured":"Joel, Z. et al. Improving mouse models for dementia. Are all the effects in tau mouse models due to overexpression? Cold Spring Harb. Symp. Quant. Biol. 83, 151\u2013161 (2018).","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"3373_CR9","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13024-017-0231-7","volume":"12","author":"JL Jankowsky","year":"2017","unstructured":"Jankowsky, J. L. & Zheng, H. Practical considerations for choosing a mouse model of Alzheimer\u2019s disease. Mol. Neurodegener. 12, 89 (2017).","journal-title":"Mol. Neurodegener."},{"key":"3373_CR10","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S1050-3862(96)00167-2","volume":"13","author":"DR Borchelt","year":"1996","unstructured":"Borchelt, D. R. et al. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet. Anal. 13, 159\u2013163 (1996).","journal-title":"Genet. Anal."},{"key":"3373_CR11","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1074\/jbc.M117.815357","volume":"293","author":"KH Strang","year":"2018","unstructured":"Strang, K. H. et al. Distinct differences in prion-like seeding and aggregation between Tau protein variants provide mechanistic insights into tauopathies. J. Biol. Chem. 293, 2408\u20132421 (2018).","journal-title":"J. Biol. Chem."},{"key":"3373_CR12","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1084\/jem.20182184","volume":"216","author":"CL Croft","year":"2019","unstructured":"Croft, C. L. et al. rAAV-based brain slice culture models of Alzheimer\u2019s and Parkinson\u2019s disease inclusion pathologies. J. Exp. Med. 216, 539\u2013555 (2019).","journal-title":"J. Exp. Med."},{"key":"3373_CR13","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1093\/hmg\/ddz151","volume":"28","author":"EJ Koller","year":"2019","unstructured":"Koller, E. J. et al. Combining P301L and S320F tau variants produces a novel accelerated model of tauopathy. Hum. Mol. Genet. 28, 3255\u20133269 (2019).","journal-title":"Hum. Mol. Genet."},{"key":"3373_CR14","doi-asserted-by":"publisher","first-page":"18488","DOI":"10.1074\/jbc.RA119.010178","volume":"294","author":"Y Xia","year":"2019","unstructured":"Xia, Y. et al. Impaired tau-microtubule interactions are prevalent among pathogenic tau variants arising from missense mutations. J. Biol. Chem. 294, 18488\u201318503 (2019).","journal-title":"J. Biol. Chem."},{"key":"3373_CR15","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1097\/00005072-199906000-00011","volume":"58","author":"O Bugiani","year":"1999","unstructured":"Bugiani, O. et al. Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau. J. Neuropathol. Exp. Neurol. 58, 667\u2013677 (1999).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"3373_CR16","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1007\/s00702-007-0632-9","volume":"114","author":"Y Baba","year":"2007","unstructured":"Baba, Y. et al. Clinical and genetic features of families with frontotemporal dementia and parkinsonism linked to chromosome 17 with a P301S tau mutation. J. Neural Transm. 114, 947\u2013950 (2007).","journal-title":"J. Neural Transm."},{"key":"3373_CR17","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/ana.10140","volume":"51","author":"SM Rosso","year":"2002","unstructured":"Rosso, S. M. et al. A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick\u2019s disease. Ann. Neurol. 51, 373\u2013376 (2002).","journal-title":"Ann. Neurol."},{"key":"3373_CR18","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1007\/s00018-014-1804-z","volume":"72","author":"V Melis","year":"2015","unstructured":"Melis, V. et al. Different pathways of molecular pathophysiology underlie cognitive and motor tauopathy phenotypes in transgenic models for Alzheimer\u2019s disease and frontotemporal lobar degeneration. Cell. Mol. Life Sci. 72, 2199\u20132222 (2015).","journal-title":"Cell. Mol. Life Sci."},{"key":"3373_CR19","doi-asserted-by":"publisher","first-page":"599","DOI":"10.2353\/ajpath.2006.060002","volume":"169","author":"K Schindowski","year":"2006","unstructured":"Schindowski, K. et al. Alzheimer\u2019s disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am. J. Pathol. 169, 599\u2013616 (2006).","journal-title":"Am. J. Pathol."},{"key":"3373_CR20","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.expneurol.2008.03.007","volume":"212","author":"H Rosenmann","year":"2008","unstructured":"Rosenmann, H. et al. A novel transgenic mouse expressing double mutant tau driven by its natural promoter exhibits tauopathy characteristics. Exp. Neurol. 212, 71\u201384 (2008).","journal-title":"Exp. Neurol."},{"key":"3373_CR21","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","volume":"39","author":"S Oddo","year":"2003","unstructured":"Oddo, S. et al. Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39, 409\u2013421 (2003).","journal-title":"Neuron"},{"key":"3373_CR22","doi-asserted-by":"publisher","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","volume":"26","author":"H Oakley","year":"2006","unstructured":"Oakley, H. et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: potential factors in amyloid plaque formation. J. Neurosci. 26, 10129\u201310140 (2006).","journal-title":"J. Neurosci."},{"key":"3373_CR23","doi-asserted-by":"publisher","unstructured":"Niesler, B., Kuerten, S., Demir, I. E. & Sch\u00e4fer, K. H. Disorders of the enteric nervous system \u2014 a holistic view. Nat. Rev. Gastroenterol. Hepatol. (2021). https:\/\/doi.org\/10.1038\/s41575-020-00385-2","DOI":"10.1038\/s41575-020-00385-2"},{"key":"3373_CR24","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.brainres.2018.01.011","volume":"1693","author":"A Chalazonitis","year":"2018","unstructured":"Chalazonitis, A. & Rao, M. Enteric nervous system manifestations of neurodegenerative disease. Brain Res. 1693, 207\u2013213 (2018).","journal-title":"Brain Res."},{"key":"3373_CR25","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1111\/j.1365-2982.2008.01134.x","volume":"20","author":"M Camilleri","year":"2008","unstructured":"Camilleri, M., Cowen, T. & Koch, T. R. Enteric neurodegeneration in ageing. Neurogastroenterol. Motil. 20, 418\u2013429 (2008).","journal-title":"Neurogastroenterol. Motil."},{"key":"3373_CR26","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s11894-010-0139-7","volume":"12","author":"B Wiskur","year":"2010","unstructured":"Wiskur, B. & Greenwood-Van Meerveld, B. The aging colon: the role of enteric neurodegeneration in constipation. Curr. Gastroenterol. Rep. 12, 507\u2013512 (2010).","journal-title":"Curr. Gastroenterol. Rep."},{"key":"3373_CR27","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/j.1440-1789.2006.00740.x","volume":"27","author":"G Bassotti","year":"2007","unstructured":"Bassotti, G. et al. Apoptotic phenomena are not a major cause of enteric neuronal loss in constipated patients with dementia. Neuropathology 27, 67\u201372 (2007).","journal-title":"Neuropathology"},{"key":"3373_CR28","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1016\/0016-5085(90)90499-Q","volume":"99","author":"PKH Tam","year":"1990","unstructured":"Tam, P. K. H. An immunohistological study of the human enteric nervous system with microtubule-associated proteins. Gastroenterology 99, 1841\u20131844 (1990).","journal-title":"Gastroenterology"},{"key":"3373_CR29","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.neulet.2018.12.031","volume":"696","author":"BN Dugger","year":"2019","unstructured":"Dugger, B. N. et al. Tau immunoreactivity in peripheral tissues of human aging and select tauopathies. Neurosci. Lett. 696, 132\u2013139 (2019).","journal-title":"Neurosci. Lett."},{"key":"3373_CR30","doi-asserted-by":"publisher","first-page":"5069","DOI":"10.1021\/pr900474t","volume":"8","author":"YM Gozal","year":"2009","unstructured":"Gozal, Y. M. et al. Proteomics analysis reveals novel components in the detergent-insoluble subproteome in Alzheimer\u2019s disease. J. Proteome Res. 8, 5069\u20135079 (2009).","journal-title":"J. Proteome Res."},{"key":"3373_CR31","doi-asserted-by":"crossref","unstructured":"Diner, I., Nguyen, T. & Seyfried, N. T. Enrichment of detergent-insoluble protein aggregates from human postmortem brain. J. Vis. Exp., 10.3791\/55835 (2017).","DOI":"10.3791\/55835"},{"key":"3373_CR32","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0304-3940(95)11484-E","volume":"189","author":"M Goedert","year":"1995","unstructured":"Goedert, M., Jakes, R. & Vanmechelen, E. Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205. Neurosci. Lett. 189, 167\u2013169 (1995).","journal-title":"Neurosci. Lett."},{"key":"3373_CR33","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1002\/jnr.490390607","volume":"39","author":"L Otvos","year":"1994","unstructured":"Otvos, L. et al. Monoclonal antibody PHF-1 recognizes tau protein phosphorylated at serine residues 396 and 404. J. Neurosci. Res. 39, 669\u2013673 (1994).","journal-title":"J. Neurosci. Res."},{"key":"3373_CR34","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1042\/bj3010871","volume":"301","author":"M Goedert","year":"1994","unstructured":"Goedert, M. et al. Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer\u2019s disease: identification of phosphorylation sites in tau protein. Biochem. J. 301, 871\u2013877 (1994).","journal-title":"Biochem. J."},{"key":"3373_CR35","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1016\/j.cell.2020.10.029","volume":"183","author":"H Wesseling","year":"2020","unstructured":"Wesseling, H. et al. Tau PTM profiles identify patient heterogeneity and stages of Alzheimer\u2019s disease. Cell 183, 1699\u20131713.e13 (2020).","journal-title":"Cell"},{"key":"3373_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13024-021-00460-5","volume":"16","author":"Y Xia","year":"2021","unstructured":"Xia, Y., Prokop, S. & Giasson, B. I. \u201cDon\u2019t Phos Over Tau\u201d: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer\u2019s disease and other tauopathies. Mol. Neurodegener. 16, 1\u201319 (2021).","journal-title":"Mol. Neurodegener."},{"key":"3373_CR37","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s40478-017-0458-0","volume":"5","author":"KH Strang","year":"2017","unstructured":"Strang, K. H. et al. Generation and characterization of new monoclonal antibodies targeting the PHF1 and AT8 epitopes on human tau. Acta Neuropathol. Commun. 5, 58 (2017).","journal-title":"Acta Neuropathol. Commun."},{"key":"3373_CR38","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1111\/j.1471-4159.2005.03181.x","volume":"94","author":"JR Babu","year":"2005","unstructured":"Babu, J. R., Geetha, T. & Wooten, M. W. Sequestosome 1\/p62 shuttles polyubiquitinated tau for proteasomal degradation. J. Neurochem. 94, 192\u2013203 (2005).","journal-title":"J. Neurochem."},{"key":"3373_CR39","doi-asserted-by":"publisher","first-page":"3033","DOI":"10.1073\/pnas.84.9.3033","volume":"84","author":"G Perry","year":"1987","unstructured":"Perry, G., Friedman, R., Shaw, G. & Chau, V. Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc. Natl Acad. Sci. USA 84, 3033\u20133036 (1987).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3373_CR40","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1046\/j.1365-2990.2002.00394.x","volume":"28","author":"E Kuusisto","year":"2002","unstructured":"Kuusisto, E., Salminen, A. & Alafuzoff, I. Early accumulation of p62 in neurofibrillary tangles in Alzheimer\u2019s disease: possible role in tangle formation. Neuropathol. Appl. Neurobiol. 28, 228\u2013237 (2002).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"3373_CR41","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/BF01923594","volume":"48","author":"R Guntern","year":"1992","unstructured":"Guntern, R., Bouras, C., Hof, P. R. & Vallet, P. G. An improved thioflavine S method for staining neurofibrillary tangles and senile plaques in Alzheimer\u2019s disease. Experientia 48, 8\u201310 (1992).","journal-title":"Experientia"},{"key":"3373_CR42","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1007\/BF00688089","volume":"7","author":"G Kel\u00e9nyi","year":"1967","unstructured":"Kel\u00e9nyi, G. Thioflavin S fluorescent and congo red anisotropic stainings in the histologic demonstration of amyloid. Acta Neuropathol. 7, 336\u2013348 (1967).","journal-title":"Acta Neuropathol."},{"key":"3373_CR43","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/0197-4580(91)90022-C","volume":"12","author":"K Iqbal","year":"1991","unstructured":"Iqbal, K., Braak, E., Braak, H., Zaidi, T. & Grundke-Iqbal, I. A silver impregnation method for labeling both Alzheimer paired helical filaments and their polypeptides separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Neurobiol. Aging 12, 357\u2013361 (1991).","journal-title":"Neurobiol. Aging"},{"key":"3373_CR44","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1179\/his.1993.16.4.335","volume":"16","author":"K Iqbal","year":"1993","unstructured":"Iqbal, K., Braak, H., Braak, E. & Grundke-Iqbal, I. Silver labeling of alzheimer neurofibrillary changes and brain \u03b2-amyloid. J. Histotechnol. 16, 335\u2013342 (1993).","journal-title":"J. Histotechnol."},{"key":"3373_CR45","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1042\/BST0381001","volume":"38","author":"K Ando","year":"2010","unstructured":"Ando, K. et al. Deletion of murine tau gene increases tau aggregation in a human mutant tau transgenic mouse model. Biochem. Soc. Trans. 38, 1001\u20131005 (2010).","journal-title":"Biochem. Soc. Trans."},{"key":"3373_CR46","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.ajpath.2010.10.034","volume":"178","author":"K Ando","year":"2011","unstructured":"Ando, K. et al. Accelerated human mutant tau aggregation by knocking out murine tau in a transgenic mouse model. Am. J. Pathol. 178, 803\u2013816 (2011).","journal-title":"Am. J. Pathol."},{"key":"3373_CR47","doi-asserted-by":"publisher","first-page":"6026","DOI":"10.1523\/JNEUROSCI.21-16-06026.2001","volume":"21","author":"T Ishihara","year":"2001","unstructured":"Ishihara, T. et al. Attenuated neurodegenerative disease phenotype in tau transgenic mouse lacking neurofilaments. J. Neurosci. 21, 6026\u20136035 (2001).","journal-title":"J. Neurosci."},{"key":"3373_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2018.00963","volume":"12","author":"M Marttinen","year":"2018","unstructured":"Marttinen, M. et al. Molecular mechanisms of synaptotoxicity and neuroinflammation in Alzheimer\u2019s disease. Front. Neurosci. 12, 1\u20139 (2018).","journal-title":"Front. Neurosci."},{"key":"3373_CR49","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","volume":"51","author":"BW Kunkle","year":"2019","unstructured":"Kunkle, B. W. et al. Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing. Nat. Genet. 51, 414\u2013430 (2019).","journal-title":"Nat. Genet."},{"key":"3373_CR50","doi-asserted-by":"publisher","first-page":"105225","DOI":"10.1016\/j.nbd.2020.105225","volume":"149","author":"A Noori","year":"2021","unstructured":"Noori, A., Mezlini, A. M., Hyman, B. T., Serrano-Pozo, A. & Das, S. Systematic review and meta-analysis of human transcriptomics reveals neuroinflammation, deficient energy metabolism, and proteostasis failure across neurodegeneration. Neurobiol. Dis. 149, 105225 (2021).","journal-title":"Neurobiol. Dis."},{"key":"3373_CR51","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1750-1326-9-24","volume":"9","author":"S Herdewyn","year":"2014","unstructured":"Herdewyn, S. et al. Prevention of intestinal obstruction reveals progressive neurodegeneration in mutant TDP-43 (A315T) mice. Mol. Neurodegener. 9, 24 (2014).","journal-title":"Mol. Neurodegener."},{"key":"3373_CR52","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41582-018-0013-z","volume":"14","author":"EE Congdon","year":"2018","unstructured":"Congdon, E. E. & Sigurdsson, E. M. Tau-targeting therapies for Alzheimer disease. Nat. Rev. Neurol. 14, 399\u2013415 (2018).","journal-title":"Nat. Rev. Neurol."},{"key":"3373_CR53","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/alzrt90","volume":"3","author":"DW Shineman","year":"2011","unstructured":"Shineman, D. W. et al. Accelerating drug discovery for Alzheimer\u2019s disease: best practices for preclinical animal studies. Alzheimer\u2019s Res. Ther. 3, 28 (2011).","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"3373_CR54","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1126\/science.1113694","volume":"309","author":"K Santacruz","year":"2005","unstructured":"Santacruz, K. et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 309, 476\u2013481 (2005).","journal-title":"Science"},{"key":"3373_CR55","doi-asserted-by":"publisher","first-page":"10637","DOI":"10.1523\/JNEUROSCI.3279-05.2005","volume":"25","author":"M Ramsden","year":"2005","unstructured":"Ramsden, M. et al. Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J. Neurosci. 25, 10637\u201310647 (2005).","journal-title":"J. Neurosci."},{"key":"3373_CR56","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","volume":"53","author":"Y Yoshiyama","year":"2007","unstructured":"Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337\u2013351 (2007).","journal-title":"Neuron"},{"key":"3373_CR57","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1101\/gr.233866.117","volume":"29","author":"LO Goodwin","year":"2019","unstructured":"Goodwin, L. O. et al. Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis. Genome Res. 29, 494\u2013505 (2019).","journal-title":"Genome Res."},{"key":"3373_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10428-1","volume":"10","author":"J Gamache","year":"2019","unstructured":"Gamache, J. et al. Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice. Nat. Commun. 10, 2479 (2019).","journal-title":"Nat. Commun."},{"key":"3373_CR59","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1523\/JNEUROSCI.2642-12.2013","volume":"33","author":"M Iba","year":"2013","unstructured":"Iba, M. et al. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer\u2019s-like tauopathy. J. Neurosci. 33, 1024\u20131037 (2013).","journal-title":"J. Neurosci."},{"key":"3373_CR60","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00401-014-1373-0","volume":"129","author":"S Boluda","year":"2015","unstructured":"Boluda, S. et al. Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer\u2019s disease or corticobasal degeneration brains. Acta Neuropathol. 129, 221\u2013237 (2015).","journal-title":"Acta Neuropathol."},{"key":"3373_CR61","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1001\/jamaneurol.2017.2822","volume":"74","author":"AL Woerman","year":"2017","unstructured":"Woerman, A. L. et al. Kinetics of human mutant tau prion formation in the brains of 2 transgenic mouse lines. JAMA Neurol. 74, 1464\u20131472 (2017).","journal-title":"JAMA Neurol."},{"key":"3373_CR62","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13024-018-0291-3","volume":"13","author":"B Zhang","year":"2018","unstructured":"Zhang, B. et al. A brain-penetrant triazolopyrimidine enhances microtubule-stability, reduces axonal dysfunction and decreases tau pathology in a mouse tauopathy model. Mol. Neurodegener. 13, 59 (2018).","journal-title":"Mol. Neurodegener."},{"key":"3373_CR63","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0896-6273(92)90117-V","volume":"8","author":"M Goedert","year":"1992","unstructured":"Goedert, M., Spillantini, M. G., Cairns, N. J. & Crowther, R. A. Tau proteins of alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8, 159\u2013168 (1992).","journal-title":"Neuron"},{"key":"3373_CR64","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s00401-015-1503-3","volume":"131","author":"S Taniguchi-Watanabe","year":"2016","unstructured":"Taniguchi-Watanabe, S. et al. Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau. Acta Neuropathol. 131, 267\u2013280 (2016).","journal-title":"Acta Neuropathol."},{"key":"3373_CR65","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41586-019-1769-z","volume":"575","author":"C Ising","year":"2019","unstructured":"Ising, C. et al. NLRP3 inflammasome activation drives tau pathology. Nature 575, 669\u2013673 (2019).","journal-title":"Nature"},{"key":"3373_CR66","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s00401-018-01957-y","volume":"137","author":"I-C Stancu","year":"2019","unstructured":"Stancu, I.-C. et al. Aggregated Tau activates NLRP3\u2013ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded Tau pathology in vivo. Acta Neuropathol. 137, 599\u2013617 (2019).","journal-title":"Acta Neuropathol."},{"key":"3373_CR67","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.3390\/cells10071652","volume":"10","author":"C Panda","year":"2021","unstructured":"Panda, C. et al. Aggregated tau-PHF6 (VQIVYK) potentiates NLRP3 inflammasome expression and autophagy in human microglial cells. Cells 10, 1652 (2021).","journal-title":"Cells"},{"key":"3373_CR68","first-page":"3","volume":"1","author":"CL Croft","year":"2021","unstructured":"Croft, C. L. et al. Photodynamic studies reveal rapid formation and appreciable turnover of tau inclusions. Acta Neuropathol. 141, 359\u2013381 (2021).","journal-title":"Acta Neuropathol."},{"key":"3373_CR69","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.expneurol.2009.07.029","volume":"223","author":"AB Rocher","year":"2010","unstructured":"Rocher, A. B. et al. Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs. Exp. Neurol. 223, 385\u2013393 (2010).","journal-title":"Exp. Neurol."},{"key":"3373_CR70","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1073\/pnas.1318807111","volume":"111","author":"KV Kuchibhotla","year":"2014","unstructured":"Kuchibhotla, K. V. et al. Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo. Proc. Natl Acad. Sci. USA 111, 510\u2013514 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3373_CR71","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1042\/BST0380967","volume":"38","author":"L Bu\u00e9e","year":"2010","unstructured":"Bu\u00e9e, L. et al. From tau phosphorylation to tau aggregation: what about neuronal death? Biochemical. Soc. Trans. 38, 967\u2013972 (2010).","journal-title":"Biochemical. Soc. Trans."},{"key":"3373_CR72","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1046\/j.1471-4159.2003.01879.x","volume":"86","author":"C Andorfer","year":"2003","unstructured":"Andorfer, C. et al. Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J. Neurochem. 86, 582\u2013590 (2003).","journal-title":"J. Neurochem."},{"key":"3373_CR73","doi-asserted-by":"publisher","first-page":"6923","DOI":"10.1073\/pnas.121119298","volume":"98","author":"AdC Alonso","year":"2001","unstructured":"Alonso, Ad. C., Zaidi, T., Novak, M., Grundke-Iqbal, I. & Iqbal, K. Hyperphosphorylation induces self-assembly of into tangles of paired helical filaments\/straight filaments. Proc. Natl Acad. Sci. USA 98, 6923\u20136928 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3373_CR74","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nm0796-783","volume":"2","author":"A Del C. Alonso","year":"1996","unstructured":"Del C. Alonso, A., Grundke-Iqbal, I. & Iqbal, K. Alzheimer\u2019s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat. Med. 2, 783\u2013787 (1996).","journal-title":"Nat. Med."},{"key":"3373_CR75","doi-asserted-by":"publisher","first-page":"11406","DOI":"10.1523\/JNEUROSCI.1230-17.2017","volume":"37","author":"S Narasimhan","year":"2017","unstructured":"Narasimhan, S. et al. Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain. J. Neurosci. 37, 11406\u201311423 (2017).","journal-title":"J. Neurosci."},{"key":"3373_CR76","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1084\/jem.20160833","volume":"213","author":"JL Guo","year":"2016","unstructured":"Guo, J. L. et al. Unique pathological tau conformers from Alzheimer\u2019s brains transmit tau pathology in nontransgenic mice. J. Exp. Med. 213, 2635\u20132654 (2016).","journal-title":"J. Exp. Med."},{"key":"3373_CR77","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1038\/s41374-019-0197-x","volume":"99","author":"KH Strang","year":"2019","unstructured":"Strang, K. H., Golde, T. E. & Giasson, B. I. MAPT mutations, tauopathy, and mechanisms of neurodegeneration. Lab. Invest. 99, 912\u2013928 (2019).","journal-title":"Lab. Invest."},{"key":"3373_CR78","doi-asserted-by":"publisher","first-page":"20309","DOI":"10.1074\/jbc.M611876200","volume":"282","author":"H Aoyagi","year":"2007","unstructured":"Aoyagi, H., Hasegawa, M. & Tamaoka, A. Fibrillogenic nuclei composed of P301L mutant tau induce elongation of P301L tau but not wild-type tau. J. Biol. Chem. 282, 20309\u201320318 (2007).","journal-title":"J. Biol. Chem."},{"key":"3373_CR79","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1093\/jnen\/60.9.872","volume":"60","author":"T Miyasaka","year":"2001","unstructured":"Miyasaka, T. et al. Selective deposition of mutant tau in the FTDP-17 brain affected by the P301L mutation. J. Neuropathol. Exp. Neurol. 60, 872\u2013884 (2001).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"3373_CR80","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1016\/S0002-9440(10)65721-5","volume":"153","author":"MG Spillantini","year":"1998","unstructured":"Spillantini, M. G., Crowther, R. A., Kamphorst, W., Heutink, P. & Van Swieten, J. C. Tau pathology in two Dutch families with mutations in the microtubule- binding region of tau. Am. J. Pathol. 153, 1359\u20131363 (1998).","journal-title":"Am. J. Pathol."},{"key":"3373_CR81","doi-asserted-by":"publisher","first-page":"4069","DOI":"10.1073\/pnas.1218497110","volume":"110","author":"F Bi","year":"2013","unstructured":"Bi, F. et al. Reactive astrocytes secrete lcn2 to promote neuron death. Proc. Natl Acad. Sci. USA 110, 4069\u20134074 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3373_CR82","doi-asserted-by":"crossref","unstructured":"Staurenghi, E. et al. Oxysterols present in Alzheimer\u2019s disease brain induce synaptotoxicity by activating astrocytes: a major role for lipocalin-2. Redox Biol. 39, 101837 (2021).","DOI":"10.1016\/j.redox.2020.101837"},{"key":"3373_CR83","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jns.2011.03.023","volume":"305","author":"J Choi","year":"2011","unstructured":"Choi, J., Lee, H.-W. & Suk, K. Increased plasma levels of lipocalin 2 in mild cognitive impairment. J. Neurol. Sci. 305, 28\u201333 (2011).","journal-title":"J. Neurol. Sci."},{"key":"3373_CR84","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1096\/fj.11-202457","volume":"26","author":"PJW Naud\u00e9","year":"2012","unstructured":"Naud\u00e9, P. J. W. et al. Lipocalin 2: novel component of proinflammatory signaling in Alzheimer\u2019s disease. FASEB J. 26, 2811\u20132823 (2012).","journal-title":"FASEB J."},{"key":"3373_CR85","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1159\/000090362","volume":"2","author":"A Papassotiropoulos","year":"2006","unstructured":"Papassotiropoulos, A. et al. Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic alzheimer\u2019s disease. Neurodegener. Dis. 2, 233\u2013241 (2006).","journal-title":"Neurodegener. Dis."},{"key":"3373_CR86","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s12031-018-1217-9","volume":"67","author":"S Bhatia","year":"2019","unstructured":"Bhatia, S., Kim, W. S., Shepherd, C. E. & Halliday, G. M. Apolipoprotein D upregulation in Alzheimer\u2019s disease but not frontotemporal dementia. J. Mol. Neurosci. 67, 125\u2013132 (2019).","journal-title":"J. Mol. Neurosci."},{"key":"3373_CR87","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1046\/j.1471-4159.1998.71041643.x","volume":"71","author":"L Terrisse","year":"2002","unstructured":"Terrisse, L. et al. Increased levels of apolipoprotein D in cerebrospinal fluid and hippocampus of Alzheimer\u2019s patients. J. Neurochem. 71, 1643\u20131650 (2002).","journal-title":"J. Neurochem."},{"key":"3373_CR88","doi-asserted-by":"crossref","unstructured":"Miyashita, A. et al. Genes associated with the progression of neurofibrillary tangles in Alzheimer\u2019s disease. Transl. Psychiatry 4, e396 (2014).","DOI":"10.1038\/tp.2014.35"},{"key":"3373_CR89","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1053\/j.gastro.2007.08.043","volume":"133","author":"CM Clarke","year":"2007","unstructured":"Clarke, C. M. et al. Visceral neuropathy and intestinal pseudo-obstruction in a murine model of a nuclear inclusion disease. Gastroenterology 133, 1971\u20131978 (2007).","journal-title":"Gastroenterology"},{"key":"3373_CR90","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/iep.12006","volume":"94","author":"MA Esmaeili","year":"2013","unstructured":"Esmaeili, M. A., Panahi, M., Yadav, S., Hennings, L. & Kiaei, M. Premature death of TDP-43 (A315T) transgenic mice due to gastrointestinal complications prior to development of full neurological symptoms of amyotrophic lateral sclerosis. Int. J. Exp. Pathol. 94, 56\u201364 (2013).","journal-title":"Int. J. Exp. Pathol."},{"key":"3373_CR91","doi-asserted-by":"crossref","unstructured":"Zhang, T. et al. Comparative epidemiological investigation of Alzheimer\u2019s disease and colorectal cancer: the possible role of gastrointestinal conditions in the pathogenesis of AD. Front. Aging Neurosci. 10, 176 (2018).","DOI":"10.3389\/fnagi.2018.00176"},{"key":"3373_CR92","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1021\/acschemneuro.9b00607","volume":"11","author":"P Fu","year":"2020","unstructured":"Fu, P., Gao, M. & Yung, K. K. L. Association of intestinal disorders with Parkinson\u2019s disease and Alzheimer\u2019s disease: a systematic review and meta-analysis. ACS Chem. Neurosci. 11, 395\u2013405 (2020).","journal-title":"ACS Chem. Neurosci."},{"key":"3373_CR93","doi-asserted-by":"publisher","first-page":"9285","DOI":"10.1096\/fj.202000414R","volume":"34","author":"A Prigent","year":"2020","unstructured":"Prigent, A. et al. Tau accumulates in Crohn\u2019s disease gut. FASEB J. 34, 9285\u20139296 (2020).","journal-title":"FASEB J."},{"key":"3373_CR94","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/nature19356","volume":"537","author":"ME Dickinson","year":"2016","unstructured":"Dickinson, M. E. et al. High-throughput discovery of novel developmental phenotypes. Nature 537, 508\u2013514 (2016).","journal-title":"Nature"},{"key":"3373_CR95","doi-asserted-by":"publisher","first-page":"e94251","DOI":"10.1371\/journal.pone.0094251","volume":"9","author":"FR Petry","year":"2014","unstructured":"Petry, F. R. et al. Specificity of anti-tau antibodies when analyzing mice models of Alzheimer\u2019s disease: problems and solutions. PLoS ONE 9, e94251 (2014).","journal-title":"PLoS ONE"},{"key":"3373_CR96","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1006\/nbdi.1999.0279","volume":"7","author":"K Duff","year":"2000","unstructured":"Duff, K. et al. Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes. Neurobiol. Dis. 7, 87\u201398 (2000).","journal-title":"Neurobiol. Dis."},{"key":"3373_CR97","doi-asserted-by":"publisher","first-page":"e0184731","DOI":"10.1371\/journal.pone.0184731","volume":"12","author":"J-KS Dhillon","year":"2017","unstructured":"Dhillon, J.-K. S. et al. A novel panel of \u03b1-synuclein antibodies reveal distinctive staining profiles in synucleinopathies. PLoS ONE 12, e0184731 (2017).","journal-title":"PLoS ONE"},{"key":"3373_CR98","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1007\/BF00308476","volume":"83","author":"PG Vallet","year":"1992","unstructured":"Vallet, P. G. et al. A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer\u2019s disease. Acta Neuropathol. 83, 170\u2013178 (1992).","journal-title":"Acta Neuropathol."},{"key":"3373_CR99","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S0896-6273(02)00682-7","volume":"34","author":"BI Giasson","year":"2002","unstructured":"Giasson, B. I. et al. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34, 521\u2013533 (2002).","journal-title":"Neuron"},{"key":"3373_CR100","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/BF00495636","volume":"81","author":"EM Rodr\u00edguez","year":"1984","unstructured":"Rodr\u00edguez, E. M., Yulis, R., Peruzzo, B., Alvial, G. & Andrade, R. Standardization of various applications of methacrylate embedding and silver methenamine for light and electron microscopy immunocytochemistry. Histochemistry 81, 253\u2013263 (1984).","journal-title":"Histochemistry"},{"key":"3373_CR101","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1093\/hmg\/ddq038","volume":"19","author":"Y-M Kuo","year":"2010","unstructured":"Kuo, Y.-M. et al. Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated \u03b1-synuclein gene mutations precede central nervous system changes. Hum. Mol. Genet. 19, 1633\u20131650 (2010).","journal-title":"Hum. Mol. Genet."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03373-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03373-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03373-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T03:58:06Z","timestamp":1669348686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03373-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3373"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-03373-1","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]},"assertion":[{"value":"1 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"TEG is a cofounder of Lacerta Therapeutics, Inc. and Andante Biologics Inc., and serves on their scientific advisory boards (SABs). He is on the SAB for Promis Neuroscience, Inc. In the past, he has served, ad hoc, on SABs related to neurodegenerative disease programs for Eli Lilly, Novartis, Bristol Myers Squib, Abbvie, Lundbeck, Biogen, and Pfizer. He has served on the medical and scientific advisory board for the Alzheimer\u2019s Association. He serves as a scientific advisor and participates in grant reviews for BrightFocus Foundation and the American Federation for Aging Research. He is a co-inventor on multiple patents and patent applications relating to AD therapeutics. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"446"}}