{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:02:50Z","timestamp":1793754170924,"version":"4.6.1"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG013854"],"award-info":[{"award-number":["P30 AG013854"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG072977"],"award-info":[{"award-number":["P30 AG072977"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG077444"],"award-info":[{"award-number":["R01 AG077444"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG056258"],"award-info":[{"award-number":["R01 AG056258"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG062566"],"award-info":[{"award-number":["R01 AG062566"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K08 AG065463"],"award-info":[{"award-number":["K08 AG065463"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01 DC008552"],"award-info":[{"award-number":["R01 DC008552"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS075075"],"award-info":[{"award-number":["R01 NS075075"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS085770"],"award-info":[{"award-number":["R01 NS085770"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["T32NS047987"],"award-info":[{"award-number":["T32NS047987"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-1842165"],"award-info":[{"award-number":["DGE-1842165"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The dentate gyrus (DG), a key hippocampal subregion in memory processing, generally resists phosphorylated tau accumulation in the amnestic dementia of the Alzheimer\u2019s type due to Alzheimer\u2019s disease (DAT-AD), but less is known about the susceptibility of the DG to other tauopathies. Here, we report stereologic densities of total DG neurons and tau inclusions in thirty-two brains of human participants with autopsy-confirmed tauopathies with distinct isoform profiles\u20143R Pick\u2019s disease (PiD, N\u2009=\u20098), 4R corticobasal degeneration (CBD, N\u2009=\u20098), 4R progressive supranuclear palsy (PSP, N\u2009=\u20098), and 3\/4R AD (N\u2009=\u20098). All participants were diagnosed during life with primary progressive aphasia (PPA), an aphasic clinical dementia syndrome characterized by progressive deterioration of language abilities with spared non-language cognitive abilities in early stages, except for five patients with DAT-AD as a comparison group. 51% of total participants were female. All specimens were stained immunohistochemically with AT8 to visualize tau pathology, and PPA cases were stained for Nissl substance to visualize neurons. Unbiased stereological analysis was performed in granule and hilar DG cells, and inclusion-to-neuron ratios were calculated. In the PPA group, PiD had highest mean total (granule\u2009+\u2009hilar) densities of DG tau pathology (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), followed by CBD, AD, then PSP. PPA-AD cases showed more inclusions in hilar cells compared to granule cells, while the opposite was true in PiD and CBD. Inclusion-to-neuron ratios revealed, on average, 33% of all DG neurons in PiD cases contained a tau inclusion, compared to\u2009~\u20097% in CBD, 2% in AD, and 0.4% in PSP. There was no significant difference between DAT-AD and PPA-AD pathologic tau burden, suggesting that differences in DG burden are not specific to clinical phenotype. We conclude that the DG is differentially vulnerable to pathologic tau accumulation, raising intriguing questions about the structural integrity and functional significance of hippocampal circuits in neurodegenerative dementias.<\/jats:p>","DOI":"10.1186\/s40478-022-01485-7","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T17:08:41Z","timestamp":1672765721000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Differential vulnerability of the dentate gyrus to tauopathies in dementias"],"prefix":"10.1186","volume":"11","author":[{"given":"Allegra","family":"Kawles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Minogue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Zouridakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Keszycki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caren","family":"Nassif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Coventry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Rogalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph","family":"Castellani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen H.","family":"Bigio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Marsel","family":"Mesulam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changiz","family":"Geula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Gefen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"1485_CR1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.bbr.2010.07.006","volume":"215","author":"RF Langston","year":"2010","unstructured":"Langston RF, Stevenson CH, Wilson CL, Saunders I, Wood ER (2010) The role of hippocampal subregions in memory for stimulus associations. Behav Brain Res 215:275\u2013291. https:\/\/doi.org\/10.1016\/j.bbr.2010.07.006","journal-title":"Behav Brain Res"},{"key":"1485_CR2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s40101-020-00225-x","volume":"39","author":"JW Seok","year":"2020","unstructured":"Seok JW, Cheong C (2020) Functional dissociation of hippocampal subregions corresponding to memory types and stages. J Physiol Anthropol 39:15. https:\/\/doi.org\/10.1186\/s40101-020-00225-x","journal-title":"J Physiol Anthropol"},{"key":"1485_CR3","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 (1995) Staging of Alzheimer\u2019s disease-related neurofibrillary changes. Neurobiol Aging 16:271\u2013278","journal-title":"Neurobiol Aging"},{"key":"1485_CR4","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.tins.2009.12.003","volume":"33","author":"SN Burke","year":"2010","unstructured":"Burke SN, Barnes CA (2010) Senescent synapses and hippocampal circuit dynamics. Trends Neurosci 33:153\u2013161. https:\/\/doi.org\/10.1016\/j.tins.2009.12.003","journal-title":"Trends Neurosci"},{"key":"1485_CR5","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/s0079-6123(02)36039-4","volume":"136","author":"JH Morrison","year":"2002","unstructured":"Morrison JH, Hof PR (2002) Selective vulnerability of corticocortical and hippocampal circuits in aging and Alzheimer\u2019s disease. Prog Brain Res 136:467\u2013486. https:\/\/doi.org\/10.1016\/s0079-6123(02)36039-4","journal-title":"Prog Brain Res"},{"key":"1485_CR6","unstructured":"Andersen P (2007) The hippocampus book. Oxford University Press, City"},{"key":"1485_CR7","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3389\/fncir.2014.00107","volume":"8","author":"P Jonas","year":"2014","unstructured":"Jonas P, Lisman J (2014) Structure, function, and plasticity of hippocampal dentate gyrus microcircuits. Front Neural Circuits 8:107. https:\/\/doi.org\/10.3389\/fncir.2014.00107","journal-title":"Front Neural Circuits"},{"key":"1485_CR8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3389\/fnana.2019.00099","volume":"13","author":"D Furcila","year":"2019","unstructured":"Furcila D, Dominguez-Alvaro M, DeFelipe J, Alonso-Nanclares L (2019) Subregional density of neurons, neurofibrillary tangles and amyloid plaques in the hippocampus of patients with alzheimer\u2019s disease. Front Neuroanat 13:99. https:\/\/doi.org\/10.3389\/fnana.2019.00099","journal-title":"Front Neuroanat"},{"key":"1485_CR9","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/ana.91","volume":"49","author":"MM Mesulam","year":"2001","unstructured":"Mesulam MM (2001) Primary progressive aphasia. Ann Neurol 49:425\u2013432","journal-title":"Ann Neurol"},{"key":"1485_CR10","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1093\/brain\/awu024","volume":"137","author":"MM Mesulam","year":"2014","unstructured":"Mesulam MM, Weintraub S, Rogalski EJ, Wieneke C, Geula C, Bigio EH (2014) Asymmetry and heterogeneity of Alzheimer\u2019s and frontotemporal pathology in primary progressive aphasia. Brain 137:1176\u20131192. https:\/\/doi.org\/10.1093\/brain\/awu024","journal-title":"Brain"},{"key":"1485_CR11","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1001\/archneur.1996.00550100158027","volume":"53","author":"JD Greene","year":"1996","unstructured":"Greene JD, Patterson K, Xuereb J, Hodges JR (1996) Alzheimer disease and nonfluent progressive aphasia. Arch Neurol 53:1072\u20131078. https:\/\/doi.org\/10.1001\/archneur.1996.00550100158027","journal-title":"Arch Neurol"},{"key":"1485_CR12","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1002\/ana.20700","volume":"59","author":"JA Knibb","year":"2006","unstructured":"Knibb JA, Xuereb JH, Patterson K, Hodges JR (2006) Clinical and pathological characterization of progressive aphasia. Ann Neurol 59:156\u2013165. https:\/\/doi.org\/10.1002\/ana.20700","journal-title":"Ann Neurol"},{"key":"1485_CR13","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1056\/NEJMra022435","volume":"349","author":"MM Mesulam","year":"2003","unstructured":"Mesulam MM (2003) Primary progressive aphasia\u2013a language-based dementia. N Engl J Med 349:1535\u20131542. https:\/\/doi.org\/10.1056\/NEJMra022435","journal-title":"N Engl J Med"},{"key":"1485_CR14","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1002\/ana.410110607","volume":"11","author":"MM Mesulam","year":"1982","unstructured":"Mesulam MM (1982) Slowly progressive aphasia without generalized dementia. Ann Neurol 11:592\u2013598. https:\/\/doi.org\/10.1002\/ana.410110607","journal-title":"Ann Neurol"},{"key":"1485_CR15","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.neurobiolaging.2010.05.020","volume":"33","author":"JD Rohrer","year":"2012","unstructured":"Rohrer JD, Rossor MN, Warren JD (2012) Alzheimer\u2019s pathology in primary progressive aphasia. Neurobiol Aging 33:744\u2013752. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2010.05.020","journal-title":"Neurobiol Aging"},{"key":"1485_CR16","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1093\/brain\/aws076","volume":"135","author":"T Gefen","year":"2012","unstructured":"Gefen T, Gasho K, Rademaker A, Lalehzari M, Weintraub S, Rogalski E, Wieneke C, Bigio E, Geula C, Mesulam MM (2012) Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain 135:1554\u20131565. https:\/\/doi.org\/10.1093\/brain\/aws076","journal-title":"Brain"},{"key":"1485_CR17","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1002\/ana.21388","volume":"63","author":"M Mesulam","year":"2008","unstructured":"Mesulam M, Wicklund A, Johnson N, Rogalski E, Leger GC, Rademaker A, Weintraub S, Bigio EH (2008) Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 63:709\u2013719. https:\/\/doi.org\/10.1002\/ana.21388","journal-title":"Ann Neurol"},{"key":"1485_CR18","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1212\/WNL.0b013e3181df0a1b","volume":"74","author":"G Gliebus","year":"2010","unstructured":"Gliebus G, Bigio EH, Gasho K, Mishra M, Caplan D, Mesulam MM, Geula C (2010) Asymmetric TDP-43 distribution in primary progressive aphasia with progranulin mutation. Neurology 74:1607\u20131610. https:\/\/doi.org\/10.1212\/WNL.0b013e3181df0a1b","journal-title":"Neurology"},{"key":"1485_CR19","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nrneurol.2009.216","volume":"6","author":"M Grossman","year":"2010","unstructured":"Grossman M (2010) Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol 6:88\u201397. https:\/\/doi.org\/10.1038\/nrneurol.2009.216","journal-title":"Nat Rev Neurol"},{"key":"1485_CR20","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1093\/brain\/awx319","volume":"141","author":"DJ Irwin","year":"2018","unstructured":"Irwin DJ, McMillan CT, Xie SX, Rascovsky K, Van Deerlin VM, Coslett HB, Hamilton R, Aguirre GK, Lee EB, Lee VMY et al (2018) Asymmetry of post-mortem neuropathology in behavioural-variant frontotemporal dementia. Brain 141:288\u2013301. https:\/\/doi.org\/10.1093\/brain\/awx319","journal-title":"Brain"},{"key":"1485_CR21","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1212\/WNL.0000000000002375","volume":"86","author":"G Kim","year":"2016","unstructured":"Kim G, Ahmadian SS, Peterson M, Parton Z, Memon R, Weintraub S, Rademaker A, Bigio E, Mesulam MM, Geula C (2016) Asymmetric pathology in primary progressive aphasia with progranulin mutations and TDP inclusions. Neurology 86:627\u2013636. https:\/\/doi.org\/10.1212\/WNL.0000000000002375","journal-title":"Neurology"},{"key":"1485_CR22","doi-asserted-by":"publisher","first-page":"e396","DOI":"10.1212\/WNL.0000000000004891","volume":"90","author":"G Kim","year":"2018","unstructured":"Kim G, Vahedi S, Gefen T, Weintraub S, Bigio EH, Mesulam MM, Geula C (2018) Asymmetric TDP pathology in primary progressive aphasia with right hemisphere language dominance. Neurology 90:e396\u2013e403. https:\/\/doi.org\/10.1212\/WNL.0000000000004891","journal-title":"Neurology"},{"key":"1485_CR23","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s12031-011-9589-0","volume":"45","author":"DW Dickson","year":"2011","unstructured":"Dickson DW, Kouri N, Murray ME, Josephs KA (2011) Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). J Mol Neurosci 45:384\u2013389. https:\/\/doi.org\/10.1007\/s12031-011-9589-0","journal-title":"J Mol Neurosci"},{"key":"1485_CR24","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1126\/science.3122323","volume":"239","author":"G Lee","year":"1988","unstructured":"Lee G, Cowan N, Kirschner M (1988) The primary structure and heterogeneity of tau protein from mouse brain. Science 239:285\u2013288. https:\/\/doi.org\/10.1126\/science.3122323","journal-title":"Science"},{"key":"1485_CR25","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/0896-6273(89)90210-9","volume":"3","author":"M Goedert","year":"1989","unstructured":"Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989) Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer\u2019s disease. Neuron 3:519\u2013526. https:\/\/doi.org\/10.1016\/0896-6273(89)90210-9","journal-title":"Neuron"},{"key":"1485_CR26","doi-asserted-by":"publisher","first-page":"S16","DOI":"10.1212\/wnl.56.suppl_4.s16","volume":"56","author":"DW Dickson","year":"2001","unstructured":"Dickson DW (2001) Neuropathology of Pick\u2019s disease. Neurology 56:S16-20. https:\/\/doi.org\/10.1212\/wnl.56.suppl_4.s16","journal-title":"Neurology"},{"key":"1485_CR27","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1002\/ana.24559","volume":"79","author":"DJ Irwin","year":"2016","unstructured":"Irwin DJ, Brettschneider J, McMillan CT, Cooper F, Olm C, Arnold SE, Van Deerlin VM, Seeley WW, Miller BL, Lee EB et al (2016) Deep clinical and neuropathological phenotyping of Pick disease. Ann Neurol 79:272\u2013287. https:\/\/doi.org\/10.1002\/ana.24559","journal-title":"Ann Neurol"},{"key":"1485_CR28","doi-asserted-by":"publisher","first-page":"e916","DOI":"10.1212\/WNL.0000000000011397","volume":"96","author":"MM Mesulam","year":"2021","unstructured":"Mesulam MM, Coventry C, Kuang A, Bigio EH, Mao Q, Flanagan ME, Gefen T, Sridhar J, Geula C, Zhang H et al (2021) Memory resilience in Alzheimer disease with primary progressive aphasia. Neurology 96:e916\u2013e925. https:\/\/doi.org\/10.1212\/WNL.0000000000011397","journal-title":"Neurology"},{"key":"1485_CR29","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/bpa.12902","volume":"31","author":"DT Ohm","year":"2021","unstructured":"Ohm DT, Fought AJ, Martersteck A, Coventry C, Sridhar J, Gefen T, Weintraub S, Bigio E, Mesulam MM, Rogalski E et al (2021) Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer\u2019s disease. Brain Pathol 31:189\u2013204. https:\/\/doi.org\/10.1111\/bpa.12902","journal-title":"Brain Pathol"},{"key":"1485_CR30","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00401-007-0237-2","volume":"114","author":"NJ Cairns","year":"2007","unstructured":"Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G et al (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114:5\u201322. https:\/\/doi.org\/10.1007\/s00401-007-0237-2","journal-title":"Acta Neuropathol"},{"key":"1485_CR31","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, Dickson DW, Duyckaerts C, Frosch MP, Masliah E et al (2012) National Institute on aging-alzheimer\u2019s association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease. Alzheimers Dement 8:1\u201313. https:\/\/doi.org\/10.1016\/j.jalz.2011.10.007","journal-title":"Alzheimers Dement"},{"key":"1485_CR32","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, Duyckaerts C, Frosch MP, Masliah E, Mirra SS et al (2012) National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach. Acta Neuropathol 123:1\u201311. https:\/\/doi.org\/10.1007\/s00401-011-0910-3","journal-title":"Acta Neuropathol"},{"key":"1485_CR33","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1002\/cne.10475","volume":"455","author":"C Geula","year":"2003","unstructured":"Geula C, Bu J, Nagykery N, Scinto LF, Chan J, Joseph J, Parker R, Wu CK (2003) Loss of calbindin-D28k from aging human cholinergic basal forebrain: relation to neuronal loss. J Comp Neurol 455:249\u2013259. https:\/\/doi.org\/10.1002\/cne.10475","journal-title":"J Comp Neurol"},{"key":"1485_CR34","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1093\/brain\/aww027","volume":"139","author":"R Ossenkoppele","year":"2016","unstructured":"Ossenkoppele R, Schonhaut DR, Scholl M, Lockhart SN, Ayakta N, Baker SL, O\u2019Neil JP, Janabi M, Lazaris A, Cantwell A et al (2016) Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer\u2019s disease. Brain 139:1551\u20131567. https:\/\/doi.org\/10.1093\/brain\/aww027","journal-title":"Brain"},{"key":"1485_CR35","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1093\/brain\/awz091","volume":"142","author":"JS Phillips","year":"2019","unstructured":"Phillips JS, Da Re F, Irwin DJ, McMillan CT, Vaishnavi SN, Xie SX, Lee EB, Cook PA, Gee JC, Shaw LM et al (2019) Longitudinal progression of grey matter atrophy in non-amnestic Alzheimer\u2019s disease. Brain 142:1701\u20131722. https:\/\/doi.org\/10.1093\/brain\/awz091","journal-title":"Brain"},{"key":"1485_CR36","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1212\/wnl.51.6.1546","volume":"51","author":"D Neary","year":"1998","unstructured":"Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M et al (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546\u20131554. https:\/\/doi.org\/10.1212\/wnl.51.6.1546","journal-title":"Neurology"},{"key":"1485_CR37","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/hipo.20255","volume":"17","author":"T Bullmann","year":"2007","unstructured":"Bullmann T, de Silva R, Holzer M, Mori H, Arendt T (2007) Expression of embryonic tau protein isoforms persist during adult neurogenesis in the hippocampus. Hippocampus 17:98\u2013102. https:\/\/doi.org\/10.1002\/hipo.20255","journal-title":"Hippocampus"},{"key":"1485_CR38","doi-asserted-by":"publisher","first-page":"921","DOI":"10.3233\/JAD-2012-112057","volume":"29","author":"M Llorens-Martin","year":"2012","unstructured":"Llorens-Martin M, Teixeira CM, Fuster-Matanzo A, Jurado-Arjona J, Borrell V, Soriano E, Avila J, Hernandez F (2012) Tau isoform with three microtubule binding domains is a marker of new axons generated from the subgranular zone in the hippocampal dentate gyrus: implications for Alzheimer\u2019s disease. J Alzheimers Dis 29:921\u2013930. https:\/\/doi.org\/10.3233\/JAD-2012-112057","journal-title":"J Alzheimers Dis"},{"key":"1485_CR39","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/ng.859","volume":"43","author":"GU Hoglinger","year":"2011","unstructured":"Hoglinger GU, Melhem NM, Dickson DW, Sleiman PM, Wang LS, Klei L, Rademakers R, de Silva R, Litvan I, Riley DE et al (2011) Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet 43:699\u2013705. https:\/\/doi.org\/10.1038\/ng.859","journal-title":"Nat Genet"},{"key":"1485_CR40","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.1212\/wnl.56.12.1702","volume":"56","author":"H Houlden","year":"2001","unstructured":"Houlden H, Baker M, Morris HR, MacDonald N, Pickering-Brown S, Adamson J, Lees AJ, Rossor MN, Quinn NP, Kertesz A et al (2001) Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 56:1702\u20131706. https:\/\/doi.org\/10.1212\/wnl.56.12.1702","journal-title":"Neurology"},{"key":"1485_CR41","doi-asserted-by":"publisher","first-page":"327","DOI":"10.3389\/fnagi.2019.00327","volume":"11","author":"P Sanchez-Juan","year":"2019","unstructured":"Sanchez-Juan P, Moreno S, de Rojas I, Hernandez I, Valero S, Alegret M, Montrreal L, Garcia Gonzalez P, Lage C, Lopez-Garcia S et al (2019) The MAPT H1 haplotype is a risk factor for Alzheimer\u2019s disease in APOE epsilon4 non-carriers. Front Aging Neurosci 11:327. https:\/\/doi.org\/10.3389\/fnagi.2019.00327","journal-title":"Front Aging Neurosci"},{"key":"1485_CR42","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.nbd.2006.10.018","volume":"25","author":"AJ Myers","year":"2007","unstructured":"Myers AJ, Pittman AM, Zhao AS, Rohrer K, Kaleem M, Marlowe L, Lees A, Leung D, McKeith IG, Perry RH et al (2007) The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts. Neurobiol Dis 25:561\u2013570. https:\/\/doi.org\/10.1016\/j.nbd.2006.10.018","journal-title":"Neurobiol Dis"},{"key":"1485_CR43","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/0306-4522(89)90424-7","volume":"31","author":"DG Amaral","year":"1989","unstructured":"Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:571\u2013591. https:\/\/doi.org\/10.1016\/0306-4522(89)90424-7","journal-title":"Neuroscience"},{"key":"1485_CR44","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/978-1-4615-6616-8_9","volume":"6","author":"DL Rosene","year":"1987","unstructured":"Rosene DL, Van Hoesen GW (1987) The hippocampal formation of the primate brain: a review of some comparative aspects of cytoarchitecture and connections. Cereb Cortex 6:345\u2013456","journal-title":"Cereb Cortex"},{"key":"1485_CR45","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/s0079-6123(08)61268-6","volume":"83","author":"GW Van Hoesen","year":"1990","unstructured":"Van Hoesen GW, Hyman BT (1990) Hippocampal formation: anatomy and the patterns of pathology in Alzheimer\u2019s disease. Prog Brain Res 83:445\u2013457. https:\/\/doi.org\/10.1016\/s0079-6123(08)61268-6","journal-title":"Prog Brain Res"},{"key":"1485_CR46","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/S0079-6123(07)63039-8","volume":"163","author":"TG Ohm","year":"2007","unstructured":"Ohm TG (2007) The dentate gyrus in Alzheimer\u2019s disease. Prog Brain Res 163:723\u2013740. https:\/\/doi.org\/10.1016\/S0079-6123(07)63039-8","journal-title":"Prog Brain Res"},{"key":"1485_CR47","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1093\/brain\/awp059","volume":"132","author":"G Lace","year":"2009","unstructured":"Lace G, Savva GM, Forster G, de Silva R, Brayne C, Matthews FE, Barclay JJ, Dakin L, Ince PG, Wharton SB et al (2009) Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based study. Brain 132:1324\u20131334. https:\/\/doi.org\/10.1093\/brain\/awp059","journal-title":"Brain"},{"key":"1485_CR48","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s00401-006-0095-3","volume":"112","author":"M Ingelsson","year":"2006","unstructured":"Ingelsson M, Ramasamy K, Cantuti-Castelvetri I, Skoglund L, Matsui T, Orne J, Kowa H, Raju S, Vanderburg CR, Augustinack JC et al (2006) No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer\u2019s disease brain. Acta Neuropathol 112:439\u2013449. https:\/\/doi.org\/10.1007\/s00401-006-0095-3","journal-title":"Acta Neuropathol"},{"key":"1485_CR49","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1007\/s004010000330","volume":"101","author":"ML Schmidt","year":"2001","unstructured":"Schmidt ML, Zhukareva V, Newell KL, Lee VM, Trojanowski JQ (2001) Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer\u2019s disease. Acta Neuropathol 101:518\u2013524. https:\/\/doi.org\/10.1007\/s004010000330","journal-title":"Acta Neuropathol"},{"key":"1485_CR50","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.neulet.2004.01.060","volume":"359","author":"Y Umeda","year":"2004","unstructured":"Umeda Y, Taniguchi S, Arima K, Piao YS, Takahashi H, Iwatsubo T, Mann D, Hasegawa M (2004) Alterations in human tau transcripts correlate with those of neurofilament in sporadic tauopathies. Neurosci Lett 359:151\u2013154. https:\/\/doi.org\/10.1016\/j.neulet.2004.01.060","journal-title":"Neurosci Lett"},{"key":"1485_CR51","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1093\/brain\/awab368","volume":"145","author":"A Kawles","year":"2022","unstructured":"Kawles A, Nishihira Y, Feldman A, Gill N, Minogue G, Keszycki R, Coventry C, Spencer C, Lilek J, Ajroud K et al (2022) Cortical and subcortical pathological burden and neuronal loss in an autopsy series of FTLD-TDP-type C. Brain 145:1069\u20131078. https:\/\/doi.org\/10.1093\/brain\/awab368","journal-title":"Brain"},{"key":"1485_CR52","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.bbr.2012.04.022","volume":"232","author":"FF Barbosa","year":"2012","unstructured":"Barbosa FF, Pontes IM, Ribeiro S, Ribeiro AM, Silva RH (2012) Differential roles of the dorsal hippocampal regions in the acquisition of spatial and temporal aspects of episodic-like memory. Behav Brain Res 232:269\u2013277. https:\/\/doi.org\/10.1016\/j.bbr.2012.04.022","journal-title":"Behav Brain Res"},{"key":"1485_CR53","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1002\/hipo.1077","volume":"11","author":"PE Gilbert","year":"2001","unstructured":"Gilbert PE, Kesner RP, Lee I (2001) Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1. Hippocampus 11:626\u2013636. https:\/\/doi.org\/10.1002\/hipo.1077","journal-title":"Hippocampus"},{"key":"1485_CR54","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s41583-019-0260-z","volume":"21","author":"T Hainmueller","year":"2020","unstructured":"Hainmueller T, Bartos M (2020) Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories. Nat Rev Neurosci 21:153\u2013168. https:\/\/doi.org\/10.1038\/s41583-019-0260-z","journal-title":"Nat Rev Neurosci"},{"key":"1485_CR55","doi-asserted-by":"publisher","first-page":"5832","DOI":"10.1073\/pnas.87.15.5832","volume":"87","author":"MF Yeckel","year":"1990","unstructured":"Yeckel MF, Berger TW (1990) Feedforward excitation of the hippocampus by afferents from the entorhinal cortex: redefinition of the role of the trisynaptic pathway. Proc Natl Acad Sci U S A 87:5832\u20135836. https:\/\/doi.org\/10.1073\/pnas.87.15.5832","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1485_CR56","doi-asserted-by":"publisher","first-page":"10574","DOI":"10.1523\/JNEUROSCI.0893-12.2012","volume":"32","author":"HJ Han","year":"2012","unstructured":"Han HJ, Allen CC, Buchovecky CM, Yetman MJ, Born HA, Marin MA, Rodgers SP, Song BJ, Lu HC, Justice MJ et al (2012) Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator. J Neurosci 32:10574\u201310586. https:\/\/doi.org\/10.1523\/JNEUROSCI.0893-12.2012","journal-title":"J Neurosci"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-022-01485-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-022-01485-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-022-01485-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T17:10:17Z","timestamp":1672765817000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-022-01485-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,3]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1485"],"URL":"https:\/\/doi.org\/10.1186\/s40478-022-01485-7","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,3]]},"assertion":[{"value":"21 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent and agreement to enter the brain donation program were obtained from all participants in the study, and the study was approved by the Northwestern University Institutional Review Board and in accordance with the Helsinki Declaration.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1"}}