{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T02:47:28Z","timestamp":1723344448669},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T00:00:00Z","timestamp":1440720000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T00:00:00Z","timestamp":1440720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Alz Res Therapy"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Alzheimer\u2019s disease (AD) is associated with neurofibrillary pathology, including neurofibrillary tangles (NFT), neuritic plaques (NP) and neuropil threads containing aggregated microtubule associated protein tau. Aggregated tau is also associated with granulovacuolar degeneration (GVD). The relationships between tau, GVD, NFT and dementia are unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We assessed hippocampal (CA1) tau-immunoreactive GVD and NFT pathology in brain donations from the population-representative Cambridge City over 75s Cohort (CC75C) using the CERAD protocol and a modified protocol that included a morphological characterisation of tau-immunoreactive deposits within neurons as NFTs or as GVD. Associations between GVD, NFT and dementia were investigated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Hippocampal pyramidal neurons affected with either NFT or GVD are common in the older population. Some tau-immunoreactive deposits resemble ghost GVD neurons. Tau immunoreactivity identified GVD in 95\u00a0% cases rated as none with haematoxylin and eosin staining. Both severe NFT (odds ratio (OR) 7.33, 95\u00a0% confidence interval (CI) 2.01; 26.80, <jats:italic>p<\/jats:italic>\u2009=\u20090.003) and severe GVD (OR 7.48, 95\u00a0%(CI) 1.54; 36.24, <jats:italic>p<\/jats:italic>\u2009=\u20090.012) were associated with dementia status. Increasing NFT (OR 2.47 95\u00a0%(CI) 1.45; 4.22, <jats:italic>p<\/jats:italic>\u2009=\u20090.001) and GVD (OR 2.12 95\u00a0%(CI) 1.23; 3.64, <jats:italic>p<\/jats:italic>\u2009=\u20090.007) severities are associated with increasing dementia severity. However, when the analyses were controlled for other neuropathologies (NFT, NP, Tar-DNA binding Protein-43 and amyloid deposits), the associations between GVD and dementia lost significance.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Current neuropathological assessments do not adequately evaluate the presence and severity of the GVD pathology and its contribution to dementia remains unclear. We recommend that protocols to assess GVD should be developed for routine use and that tau, in a non-PHF associated conformation, is reliably associated with GVD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13195-015-0141-2","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T05:55:24Z","timestamp":1440654924000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Re-examining tau-immunoreactive pathology in the population: granulovacuolar degeneration and neurofibrillary tangles"],"prefix":"10.1186","volume":"7","author":[{"given":"Sally","family":"Hunter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thais","family":"Minett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuomo","family":"Polvikoski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeta","family":"Mukaetova-Ladinska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Brayne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Cambridge City over-75s Cohort Collaboration","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,8,28]]},"reference":[{"key":"141_CR1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1212\/WNL.39.9.1159","volume":"39","author":"JC Morris","year":"1989","unstructured":"Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989;39:1159\u201365.","journal-title":"Neurology"},{"key":"141_CR2","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1212\/WNL.41.4.479","volume":"41","author":"SS Mirra","year":"1991","unstructured":"Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41:479\u201386.","journal-title":"Neurology"},{"key":"141_CR3","unstructured":"Consortium to Establish a Registry for Alzheimer Disease Neuropathological Assessment. http:\/\/cerad.mc.duke.edu\/Neuropathology.htm. Accessed 24\/08\/2015."},{"key":"141_CR4","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239\u201359.","journal-title":"Acta Neuropathol."},{"key":"141_CR5","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","volume":"112","author":"H Braak","year":"2006","unstructured":"Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112:389\u2013404.","journal-title":"Acta Neuropathol."},{"key":"141_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","volume":"8","author":"BT Hyman","year":"2012","unstructured":"Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012;8:1\u201313.","journal-title":"Alzheimers Dement."},{"key":"141_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","volume":"123","author":"TJ Montine","year":"2012","unstructured":"Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 2012;123:1\u201311.","journal-title":"Acta Neuropathol."},{"key":"141_CR8","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","volume":"16","author":"H Braak","year":"1995","unstructured":"Braak H, Braak E. Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol Aging. 1995;16:271\u20138. discussion 278\u201384.","journal-title":"Neurobiol Aging."},{"key":"141_CR9","doi-asserted-by":"publisher","first-page":"5842","DOI":"10.1073\/pnas.88.13.5842","volume":"88","author":"CR Harrington","year":"1991","unstructured":"Harrington CR, Mukaetova-Ladinska EB, Hills R, Edwards PC, Montejo De Garcini E, Novak M, et al. Measurement of distinct immunochemical presentations of tau protein in Alzheimer disease. Proc Natl Acad Sci U S A. 1991;88:5842\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"141_CR10","first-page":"711","volume":"137","author":"W Bondareff","year":"1990","unstructured":"Bondareff W, Wischik CM, Novak M, Amos WB, Klug A, Roth M. Molecular analysis of neurofibrillary degeneration in Alzheimer's disease. An immunohistochemical study. Am J Pathol. 1990;137:711\u201323.","journal-title":"Am J Pathol"},{"key":"141_CR11","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s007020050096","volume":"105","author":"H Braak","year":"1998","unstructured":"Braak H, Braak E. Argyrophilic grain disease: frequency of occurrence in different age categories and neuropathological diagnostic criteria. J Neural Transm. 1998;105:801\u201319.","journal-title":"J Neural Transm."},{"key":"141_CR12","first-page":"641","volume":"139","author":"W Bondareff","year":"1991","unstructured":"Bondareff W, Wischik CM, Novak M, Roth M. Sequestration of tau by granulovacuolar degeneration in Alzheimer's disease. Am J Pathol. 1991;139:641\u20137.","journal-title":"Am J Pathol."},{"key":"141_CR13","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1007\/BF00686619","volume":"73","author":"DW Dickson","year":"1987","unstructured":"Dickson DW, Ksiezak-Reding H, Davies P, Yen SH. A monoclonal antibody that recognizes a phosphorylated epitope in Alzheimer neurofibrillary tangles, neurofilaments and tau proteins immunostains granulovacuolar degeneration. Acta Neuropathol. 1987;73:254\u20138.","journal-title":"Acta Neuropathol."},{"key":"141_CR14","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/j.1440-1819.1996.tb01678.x","volume":"50","author":"K Ikegami","year":"1996","unstructured":"Ikegami K, Kimura T, Katsuragi S, Ono T, Yamamoto H, Miyamoto E, et al. Immunohistochemical examination of phosphorylated tau in granulovacuolar degeneration granules. Psychiatry Clin Neurosci. 1996;50:137\u201340.","journal-title":"Psychiatry Clin Neurosci."},{"key":"141_CR15","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00401-011-0871-6","volume":"122","author":"DR Thal","year":"2011","unstructured":"Thal DR, Del Tredici K, Ludolph AC, Hoozemans JJ, Rozemuller AJ, Braak H, et al. Stages of granulovacuolar degeneration: their relation to Alzheimer's disease and chronic stress response. Acta Neuropathol. 2011;122:577\u201389.","journal-title":"Acta Neuropathol."},{"key":"141_CR16","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00401-002-0581-1","volume":"104","author":"M Holzer","year":"2002","unstructured":"Holzer M, Gartner U, Stobe A, Hartig W, Gruschka H, Bruckner MK, et al. Inverse association of Pin1 and tau accumulation in Alzheimer's disease hippocampus. Acta Neuropathol. 2002;104:471\u201381.","journal-title":"Acta Neuropathol."},{"key":"141_CR17","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1097\/00005072-198807000-00001","volume":"47","author":"S Love","year":"1988","unstructured":"Love S, Saitoh T, Quijada S, Cole GM, Terry RD. Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangles, Pick bodies and Lewy bodies. J Neuropathol Exp Neurol. 1988;47:393\u2013405.","journal-title":"J Neuropathol Exp Neurol."},{"key":"141_CR18","unstructured":"Simchowicz T. Histologische Studien uber die senile Demenz. Histologische und histopathologische Arbeiten uber die Grosshirnrinde (Histological studies of senile dementia. Histological and histopathological work over the cerebral cortex.). 1911;4:267\u2013444."},{"key":"141_CR19","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1007\/BF00296544","volume":"82","author":"K Okamoto","year":"1991","unstructured":"Okamoto K, Hirai S, Iizuka T, Yanagisawa T, Watanabe M. Reexamination of granulovacuolar degeneration. Acta Neuropathol. 1991;82:340\u20135.","journal-title":"Acta Neuropathol."},{"key":"141_CR20","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s004010050477","volume":"91","author":"R Mena","year":"1996","unstructured":"Mena R, Edwards PC, Harrington CR, Mukaetova-Ladinska EB, Wischik CM. Staging the pathological assembly of truncated tau protein into paired helical filaments in Alzheimer's disease. Acta Neuropathol. 1996;91:633\u201341.","journal-title":"Acta Neuropathol."},{"key":"141_CR21","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1097\/00005072-197705000-00006","volume":"36","author":"MJ Ball","year":"1977","unstructured":"Ball MJ, Lo P. Granulovacuolar degeneration in the ageing brain and in dementia. J Neuropathol Exp Neurol. 1977;36:474\u201387.","journal-title":"J Neuropathol Exp Neurol."},{"key":"141_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00304627","volume":"85","author":"M Xu","year":"1992","unstructured":"Xu M, Shibayama H, Kobayashi H, Yamada K, Ishihara R, Zhao P, et al. Granulovacuolar degeneration in the hippocampal cortex of aging and demented patients\u2014a quantitative study. Acta Neuropathol. 1992;85:1\u20139.","journal-title":"Acta Neuropathol."},{"key":"141_CR23","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/path.1711060305","volume":"106","author":"BE Tomlinson","year":"1972","unstructured":"Tomlinson BE, Kitchener D. Granulovacuolar degeneration of hippocampal pyramidal cells. J Pathol. 1972;106:165\u201385.","journal-title":"J Pathol."},{"key":"141_CR24","doi-asserted-by":"publisher","first-page":"e26996","DOI":"10.1371\/journal.pone.0026996","volume":"6","author":"Y Yamazaki","year":"2011","unstructured":"Yamazaki Y, Matsubara T, Takahashi T, Kurashige T, Dohi E, Hiji M, et al. Granulovacuolar degenerations appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders. PLoS ONE. 2011;6:e26996.","journal-title":"PLoS ONE."},{"key":"141_CR25","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/S0197-4580(00)00110-X","volume":"21","author":"C Schwab","year":"2000","unstructured":"Schwab C, DeMaggio AJ, Ghoshal N, Binder LI, Kuret J, McGeer PL. Casein kinase 1 delta is associated with pathological accumulation of tau in several neurodegenerative diseases. Neurobiol Aging. 2000;21:503\u201310.","journal-title":"Neurobiol Aging."},{"key":"141_CR26","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/BF00690983","volume":"42","author":"DM Mann","year":"1978","unstructured":"Mann DM. Granulovacuolar degeneration in pyramidal cells of the hippocampus. Acta Neuropathol. 1978;42:149\u201351.","journal-title":"Acta Neuropathol."},{"key":"141_CR27","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/BF00690970","volume":"42","author":"MJ Ball","year":"1978","unstructured":"Ball MJ. Topographic distribution of neurofibrillary tangles and granulovacuolar degeneration in hippocampal cortex of aging and demented patients. A quantitative study. Acta Neuropathol. 1978;42:73\u201380.","journal-title":"Acta Neuropathol"},{"key":"141_CR28","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3233\/JAD-2011-111268","volume":"28","author":"HA Keage","year":"2012","unstructured":"Keage HA, Ince PG, Matthews FE, Wharton SB, McKeith IG, Brayne C, et al. Cc75C: Impact of less common and \u2018disregarded\u2019 neurodegenerative pathologies on dementia burden in a population-based cohort. J Alzheimers Dis. 2012;28:485\u201393.","journal-title":"J Alzheimers Dis."},{"key":"141_CR29","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1093\/ije\/dyl293","volume":"36","author":"J Fleming","year":"2007","unstructured":"Fleming J, Zhao E, O'Connor DW, Pollitt PA, Brayne C. Cohort profile: the Cambridge City over-75s Cohort (CC75C). Int J Epidemiol. 2007;36:40\u20136.","journal-title":"Int J Epidemiol."},{"key":"141_CR30","volume-title":"Diagnostic and statistical manual of mental disorders. DSM-III-R","author":"APA","year":"1987","unstructured":"APA. Diagnostic and statistical manual of mental disorders. DSM-III-R. Washington: American Psychiatric Association; 1987."},{"key":"141_CR31","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1192\/bjp.149.6.698","volume":"149","author":"M Roth","year":"1986","unstructured":"Roth M, Tym E, Mountjoy CQ, Huppert FA, Hendrie H, Verma S, et al. CAMDEX. A standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry. 1986;149:698\u2013709.","journal-title":"Br J Psychiatry"},{"key":"141_CR32","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1134108","volume":"314","author":"M Neumann","year":"2006","unstructured":"Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314:130\u20133.","journal-title":"Science."},{"key":"141_CR33","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/ana.20203","volume":"56","author":"JR Hodges","year":"2004","unstructured":"Hodges JR, Davies RR, Xuereb JH, Casey B, Broe M, Bak TH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol. 2004;56:399\u2013406.","journal-title":"Ann Neurol."},{"key":"141_CR34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1348\/000711006X126600","volume":"61","author":"KL Gwet","year":"2008","unstructured":"Gwet KL. Computing inter-rater reliability and its variance in the presence of high agreement. Br J Math Stat Psychol. 2008;61:29\u201348.","journal-title":"Br J Math Stat Psychol."},{"key":"141_CR35","doi-asserted-by":"publisher","first-page":"159","DOI":"10.2307\/2529310","volume":"33","author":"JR Landis","year":"1977","unstructured":"Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159\u201374.","journal-title":"Biometrics."},{"key":"141_CR36","doi-asserted-by":"publisher","first-page":"271","DOI":"10.5414\/NPP29271","volume":"29","author":"GG Kovacs","year":"2010","unstructured":"Kovacs GG, Budka H. Current concepts of neuropathological diagnostics in practice: neurodegenerative diseases. Clin Neuropathol. 2010;29:271\u201388.","journal-title":"Clin Neuropathol."},{"key":"141_CR37","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/S0306-4522(02)00942-9","volume":"117","author":"T Bussiere","year":"2003","unstructured":"Bussiere T, Gold G, Kovari E, Giannakopoulos P, Bouras C, Perl DP, et al. Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer's disease. Neuroscience. 2003;117:577\u201392.","journal-title":"Neuroscience."},{"key":"141_CR38","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/0006-8993(86)91077-2","volume":"385","author":"DL Price","year":"1986","unstructured":"Price DL, Altschuler RJ, Struble RG, Casanova MF, Cork LC, Murphy DB. Sequestration of tubulin in neurons in Alzheimer's disease. Brain Res. 1986;385:305\u201310.","journal-title":"Brain Res."},{"key":"141_CR39","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1038\/labinvest.2011.149","volume":"91","author":"RJ Castellani","year":"2011","unstructured":"Castellani RJ, Gupta Y, Sheng B, Siedlak SL, Harris PL, Coller JM, et al. A novel origin for granulovacuolar degeneration in aging and Alzheimer's disease: parallels to stress granules. Lab Invest. 2011;91:1777\u201386.","journal-title":"Lab Invest."},{"key":"141_CR40","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/BF00692056","volume":"37","author":"MJ Ball","year":"1977","unstructured":"Ball MJ. Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study. Acta Neuropathol. 1977;37:111\u20138.","journal-title":"Acta Neuropathol"},{"key":"141_CR41","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.neulet.2009.06.024","volume":"463","author":"A Kadokura","year":"2009","unstructured":"Kadokura A, Yamazaki T, Kakuda S, Makioka K, Lemere CA, Fujita Y, et al. Phosphorylation-dependent TDP-43 antibody detects intraneuronal dot-like structures showing morphological characters of granulovacuolar degeneration. Neurosci Lett. 2009;463:87\u201392.","journal-title":"Neurosci Lett."},{"key":"141_CR42","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.nbd.2014.07.006","volume":"71","author":"C Kohler","year":"2014","unstructured":"Kohler C, Dinekov M, Gotz J. Granulovacuolar degeneration and unfolded protein response in mouse models of tauopathy and Abeta amyloidosis. Neurobiol Dis. 2014;71:169\u201379.","journal-title":"Neurobiol Dis."},{"key":"141_CR43","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/2051-5960-2-22","volume":"2","author":"H Lund","year":"2014","unstructured":"Lund H, Gustafsson E, Svensson A, Nilsson M, Berg M, Sunnemark D, et al. MARK4 and MARK3 associate with early tau phosphorylation in Alzheimer's disease granulovacuolar degeneration bodies. Acta Neuropathol Commun. 2014;2:22.","journal-title":"Acta Neuropathol Commun."},{"key":"141_CR44","doi-asserted-by":"publisher","first-page":"32789","DOI":"10.1074\/jbc.271.51.32789","volume":"271","author":"G Carmel","year":"1996","unstructured":"Carmel G, Mager EM, Binder LI, Kuret J. The structural basis of monoclonal antibody Alz50's selectivity for Alzheimer's disease pathology. J Biol Chem. 1996;271:32789\u201395.","journal-title":"J Biol Chem."},{"key":"141_CR45","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/BF00296369","volume":"81","author":"H Yamaguchi","year":"1991","unstructured":"Yamaguchi H, Nakazato Y, Kawarabayashi T, Ishiguro K, Ihara Y, Morimatsu M, et al. Extracellular neurofibrillary tangles associated with degenerating neurites and neuropil threads in Alzheimer-type dementia. Acta Neuropathol. 1991;81:603\u20139.","journal-title":"Acta Neuropathol."}],"container-title":["Alzheimer's Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-015-0141-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13195-015-0141-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-015-0141-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-015-0141-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T23:26:31Z","timestamp":1643585191000},"score":1,"resource":{"primary":{"URL":"https:\/\/alzres.biomedcentral.com\/articles\/10.1186\/s13195-015-0141-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,28]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["141"],"URL":"https:\/\/doi.org\/10.1186\/s13195-015-0141-2","relation":{},"ISSN":["1758-9193"],"issn-type":[{"type":"electronic","value":"1758-9193"}],"subject":[],"published":{"date-parts":[[2015,8,28]]},"assertion":[{"value":"16 December 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"57"}}