{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:50:51Z","timestamp":1791859851654,"version":"4.3.4"},"reference-count":129,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100017518","name":"Hans und Ilse Breuer-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017518","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008977","name":"Universit\u00e4t Ulm","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008977","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Sporadic Alzheimer\u2019s disease (AD) involves specific neuronal types and progresses in a systematic manner, permitting subdivision into six neuropathological stages. Neurofibrillary tangle (NFT) stages I\u2013III display abnormal tau inclusions confined to subcortical nuclei and temporal allocortical regions, frequently without amyloid \u03b2 (A\u03b2) deposition. We previously suggested a sequence of neuronal involvement in AD that could proceed from entorhinal pre-\u03b1 cells to hippocampal prosubicular pyramidal cells and the CA1\/CA2 sectors, from there to the thorny excrescences on mossy cells in CA3\/CA4, and, finally, from the mossy cells to dentate fascia (Fd) granular cells. Here, we aimed to see if associations existed between the early NFT stages I\u2013III, when A\u03b2 deposits are frequently absent, and the following four categories: (1)\u00a0anatomical regions and abnormal morphological tau changes in region-specific layers, (2) nerve cell loss, (3) APOE genotype, and (4) the trajectory (directionality) of tau progression in the hippocampal formation. To do so, we examined the transentorhinal\/entorhinal regions and hippocampal formation using AT8-immunohistochemistry in 100\u00a0\u00b5m sections from <jats:italic>N<\/jats:italic>\u2009=\u2009308 brains with tau inclusions lacking A\u03b2 deposits between NFT stages I and III (average age at death 66.7\u00a0years for females, 66.4\u00a0years for males). Our results indicated a significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) ordered progression of abnormal tau in a direction opposite to currently known unidirectional intrahippocampal connections, thereby indirectly supporting the idea of transneuronal abnormal tau spreading, i.e., anterogradely, through the hippocampal formation. Tau-related neuronal loss was also significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 for the transentorhinal\/entorhinal regions and for sectors CA1\/CA2 and <jats:italic>p<\/jats:italic>\u2009=\u20090.003 for CA3\/CA4\/Fd). These findings challenge the amyloid cascade and the PART hypotheses, corroborating the concept that early AD-related tau inclusions and tau-related neuronal loss occur independently of A\u03b2 deposition.<\/jats:p>","DOI":"10.1007\/s00401-025-02862-x","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:47:14Z","timestamp":1747982834000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Sequence and trajectory of early Alzheimer\u2019s disease-related tau inclusions in the hippocampal formation of cases without amyloid-\u03b2 deposits"],"prefix":"10.1007","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6776-1045","authenticated-orcid":false,"given":"Heiko","family":"Braak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-9006","authenticated-orcid":false,"given":"Benjamin","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0470-0063","authenticated-orcid":false,"given":"Simone","family":"Feldengut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8905-1810","authenticated-orcid":false,"given":"Michael","family":"Sch\u00f6n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9130-7838","authenticated-orcid":false,"given":"Kelly","family":"Del Tredici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"2862_CR1","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1007\/s00401-014-1254-6","volume":"127","author":"Z Ahmed","year":"2014","unstructured":"Ahmed Z, Cooper J, Murray TK, Garn K, McNaughton E, Clark H et al (2014) A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: the pattern of spread is determined by connectivity, not proximity. Acta Neuropathol 127:667\u2013683. https:\/\/doi.org\/10.1007\/s00401-014-1254-6","journal-title":"Acta Neuropathol"},{"key":"2862_CR2","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1111\/j.1750-3639.2008.00147.x","volume":"18","author":"I Alafuzoff","year":"2008","unstructured":"Alafuzoff I, Arzberger T, Al-Sarraj S, Bodi I, Bogdanovic N, Braak H et al (2008) Staging of neurofibrillary pathology in Alzheimer\u2019s disease: a study for the BrainNet Europe Consortium. Brain Pathol 18:484\u2013496. https:\/\/doi.org\/10.1111\/j.1750-3639.2008.00147.x","journal-title":"Brain Pathol"},{"key":"2862_CR3","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/s0197-4580(00)00216-5","volume":"21","author":"T Arendt","year":"2000","unstructured":"Arendt T (2000) Alzheimer\u2019s disease as a loss of differentiation control in a subset of neurons that retain immature features in the adult brain. Neurobiol Aging 21:783\u2013796. https:\/\/doi.org\/10.1016\/s0197-4580(00)00216-5","journal-title":"Neurobiol Aging"},{"key":"2862_CR4","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/jnc.14036","volume":"143","author":"T Arendt","year":"2017","unstructured":"Arendt T, Stieler J, Ueberham U (2017) Is sporadic Alzheimer\u2019s disease a developmental disorder? J Neurochem 143:396\u2013408. https:\/\/doi.org\/10.1111\/jnc.14036","journal-title":"J Neurochem"},{"key":"2862_CR5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/alz.12192","volume":"17","author":"A Arnsten","year":"2021","unstructured":"Arnsten A, Datta D, Del Tredici K, Braak H (2021) Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer\u2019s disease. Alzheimer\u2019s Dement 17:115\u2013124. https:\/\/doi.org\/10.1002\/alz.12192","journal-title":"Alzheimer\u2019s Dement"},{"issue":"4","key":"2862_CR6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3389\/fnhum.2010.00042","volume":"28","author":"JC Augustinack","year":"2010","unstructured":"Augustinack JC, Helmer K, Huber KE, Kakunoori S, Z\u00f6llei L, Fischl B (2010) Direct visualization of the perforant pathway in the human brain with ex vivo diffusion tensor imaging. Front Hum Neurosci 28(4):42. https:\/\/doi.org\/10.3389\/fnhum.2010.00042","journal-title":"Front Hum Neurosci"},{"key":"2862_CR7","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.neuron.2019.01.056","volume":"101","author":"ME Belloy","year":"2019","unstructured":"Belloy ME, Napolioni V, Greicius MD (2019) A quarter century of APOE and Alzheimer\u2019s disease: progress to date and the path forward. Neuron 101:820\u2013838. https:\/\/doi.org\/10.1016\/j.neuron.2019.01.056","journal-title":"Neuron"},{"key":"2862_CR8","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1093\/brain\/awz193","volume":"142","author":"MJ Betts","year":"2019","unstructured":"Betts MJ, Kirilina E, Otaduy MCG, Ivanov D, Acosta-Cabronero J, Callaghan MF et al (2019) Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases. Brain 142:2558\u20132571. https:\/\/doi.org\/10.1093\/brain\/awz193","journal-title":"Brain"},{"key":"2862_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JAD-2011-110659","volume":"23","author":"L Blazquez-Llorca","year":"2011","unstructured":"Blazquez-Llorca L, Garcia-Marin V, Merino-Serrais P, Avila J, DeFelipe J (2011) Abnormal tau phosphorylation in the thorny excrescences of CA3 hippocampal neurons in patients with Alzheimer\u2019s disease. J Alzheimer Dis 23:1\u201316. https:\/\/doi.org\/10.3233\/JAD-2011-110659","journal-title":"J Alzheimer Dis"},{"key":"2862_CR10","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/s004010050622","volume":"93","author":"E Braak","year":"1997","unstructured":"Braak E, Braak H (1997) Alzheimer\u2019s disease: transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon\u2019s horn. Acta Neuropathol 93:323\u2013325. https:\/\/doi.org\/10.1007\/s004010050622","journal-title":"Acta Neuropathol"},{"key":"2862_CR11","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/BF00293315","volume":"87","author":"E Braak","year":"1994","unstructured":"Braak E, Braak H, Mandelkow EM (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87:554\u2013567. https:\/\/doi.org\/10.1007\/BF00293315","journal-title":"Acta Neuropathol"},{"key":"2862_CR12","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-81522-5","volume-title":"Architectonics of the human telencephalic cortex","author":"H Braak","year":"1980","unstructured":"Braak H (1980) Architectonics of the human telencephalic cortex. Springer, Berlin"},{"key":"2862_CR13","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/BF00690836","volume":"68","author":"H Braak","year":"1985","unstructured":"Braak H, Braak E (1985) On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer\u2019s disease. Acta Neuropathol 68:325\u2013332. https:\/\/doi.org\/10.1007\/BF00690836","journal-title":"Acta Neuropathol"},{"key":"2862_CR14","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0304-3940(86)90288-0","volume":"65","author":"H Braak","year":"1986","unstructured":"Braak H, Braak E, Grundke-Iqbal I, Iqbal K (1986) Occurrence of neuropil threads in the senile human brain and in Alzheimer\u2019s disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65:351\u2013351","journal-title":"Neurosci Lett"},{"key":"2862_CR15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1365-2990.1988.tb00864.x","volume":"14","author":"H Braak","year":"1988","unstructured":"Braak H, Braak E (1988) Neuropil threads occur in dendrites of tangle-bearing nerve cells. Neuropathol Appl Neurobiol 14:39\u201344. https:\/\/doi.org\/10.1111\/j.1365-2990.1988.tb00864.x","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2862_CR16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/0304-3940(87)90204-7","volume":"76","author":"H Braak","year":"1987","unstructured":"Braak H, Braak E (1987) Argyrophilic grains: characteristic pathology of cerebral cortex in cases of adult onset dementia without Alzheimer changes. Neurosci Lett 76:124\u2013127. https:\/\/doi.org\/10.1016\/0304-3940(87)90204-7","journal-title":"Neurosci Lett"},{"key":"2862_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1365-2990.1989.tb01146.x","volume":"15","author":"H Braak","year":"1989","unstructured":"Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15:13\u201326. https:\/\/doi.org\/10.1111\/j.1365-2990.1989.tb01146.x","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2862_CR18","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239\u2013259. https:\/\/doi.org\/10.1007\/BF00308809","journal-title":"Acta Neuropathol"},{"key":"2862_CR19","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1750-3639.1991.tb00661.x","volume":"1","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Pathol 1:213\u2013216. https:\/\/doi.org\/10.1111\/j.1750-3639.1991.tb00661.x","journal-title":"Brain Pathol"},{"key":"2862_CR20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/0168-0102(92)90014-4","volume":"15","author":"H Braak","year":"1992","unstructured":"Braak H, Braak E (1992) The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases. Neurosci Res 15:6\u201331. https:\/\/doi.org\/10.1016\/0168-0102(92)90014-4","journal-title":"Neurosci Res"},{"key":"2862_CR21","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00401-010-0789-4","volume":"121","author":"H Braak","year":"2011","unstructured":"Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer\u2019s disease in individuals under thirty. Acta Neuropathol 121:171\u2013181. https:\/\/doi.org\/10.1007\/s00401-010-0789-4","journal-title":"Acta Neuropathol"},{"key":"2862_CR22","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1007\/s00401-014-1356-1","volume":"128","author":"H Braak","year":"2014","unstructured":"Braak H, Del Tredici K (2014) Are cases with tau pathology occurring in the absence of A\u03b2 deposits part of the AD-related pathological process? Acta Neuropathol 128:767\u2013772. https:\/\/doi.org\/10.1007\/s00401-014-1356-1","journal-title":"Acta Neuropathol"},{"key":"2862_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-12679-1_1","volume":"215","author":"H Braak","year":"2015","unstructured":"Braak H, Del Tredici K (2015) Neuroanatomy and pathology of sporadic Alzheimer\u2019s disease. Adv Anat Embryol Cell Biol 215:1\u2013162","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"2862_CR24","doi-asserted-by":"publisher","first-page":"3372","DOI":"10.1093\/cercor\/bhy152","volume":"28","author":"H Braak","year":"2018","unstructured":"Braak H, Del Tredici K (2018) Spreading of tau pathology in sporadic Alzheimer\u2019s disease along cortico-cortical top-down connections. Cereb Cortex 28:3372\u20133384. https:\/\/doi.org\/10.1093\/cercor\/bhy152","journal-title":"Cereb Cortex"},{"key":"2862_CR25","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/jnen\/nlz123","volume":"79","author":"H Braak","year":"2020","unstructured":"Braak H, Del Tredici K (2020) From the entorhinal region via the prosubiculum to the dentate fascia: Alzheimer disease-related neurofibrillary changes in the temporal allocortex. J Neuropathol Exp Neurol 79:163\u2013175. https:\/\/doi.org\/10.1093\/jnen\/nlz123","journal-title":"J Neuropathol Exp Neurol"},{"key":"2862_CR26","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 (2006) Staging of Alzheimer\u2019s disease-associated neurofibrillary pathology using paraffin sections and immunohistochemistry. Acta Neuropathol 112:389\u2013404. https:\/\/doi.org\/10.1007\/s00401-006-0127-z","journal-title":"Acta Neuropathol"},{"key":"2862_CR27","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","volume":"70","author":"H Braak","year":"2011","unstructured":"Braak H, Thal DR, Ghebremedhin E, Del Tredici K (2011) Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 70:960\u2013969. https:\/\/doi.org\/10.1097\/NEN.0b013e318232a379","journal-title":"J Neuropathol Exp Neurol"},{"key":"2862_CR28","doi-asserted-by":"publisher","first-page":"2989","DOI":"10.4081\/ejh.2018.2989","volume":"62","author":"H Braak","year":"2018","unstructured":"Braak H, Feldengut S, Kassubek J, Yilmazer-Hanke D, Del Tredici K (2018) Two histological methods for recognition and study of cortical microinfarctions in thick sections. Eur J Histochem 62:2989. https:\/\/doi.org\/10.4081\/ejh.2018.2989","journal-title":"Eur J Histochem"},{"key":"2862_CR29","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.neuron.2011.02.006","volume":"69","author":"T Branco","year":"2011","unstructured":"Branco T, H\u00e4usser M (2011) Synaptic integration gradients in single cortical pyramidal cell dendrites. Neuron 69:885\u2013892. https:\/\/doi.org\/10.1016\/j.neuron.2011.02.006","journal-title":"Neuron"},{"key":"2862_CR30","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nrn3887","volume":"16","author":"J Brettschneider","year":"2015","unstructured":"Brettschneider J, Del Tredici K, Lee VMY, Trojanowski JQ (2015) Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci 16:109\u2013120. https:\/\/doi.org\/10.1038\/nrn3887","journal-title":"Nat Rev Neurosci"},{"key":"2862_CR31","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/nrm2873","volume":"11","author":"P Brundin","year":"2010","unstructured":"Brundin P, Melki R, Kopito R (2010) Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol 11:301\u2013307. https:\/\/doi.org\/10.1038\/nrm2873","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2862_CR32","first-page":"678","volume":"13","author":"SK Campbell","year":"1987","unstructured":"Campbell SK, Switzer RC, Martin TL (1987) Alzheimer\u2019s plaques and tangles: A controlled and enhanced silver staining method. Soc Neurosci Abstr 13:678","journal-title":"Soc Neurosci Abstr"},{"key":"2862_CR33","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1126\/science.8346443","volume":"261","author":"EH Corder","year":"1993","unstructured":"Corder EH, Saunders AM, Strittmacher WJ, Schmechel DE, Gaskell PC, Small GW et al (1993) Gene dose of apolipoprotein E and type 4 allele and the risk of Alzheimer\u2019s disease in late-onset families. Science 261:921\u2013923. https:\/\/doi.org\/10.1126\/science.8346443","journal-title":"Science"},{"key":"2862_CR34","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/ng0694-180","volume":"7","author":"EH Corder","year":"1994","unstructured":"Corder EH, Saunders AM, Risch NJ, Schmechel DE, Gaskell PC Jr et al (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet 7:180\u2013184. https:\/\/doi.org\/10.1038\/ng0694-180","journal-title":"Nat Genet"},{"key":"2862_CR35","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s00401-014-1349-0","volume":"128","author":"JF Crary","year":"2014","unstructured":"Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I et al (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755\u2013766. https:\/\/doi.org\/10.1007\/s00401-014-1349-0","journal-title":"Acta Neuropathol"},{"key":"2862_CR36","doi-asserted-by":"publisher","first-page":"53","DOI":"10.29245\/2572.942x\/2016\/6.1059","volume":"1","author":"JF Crary","year":"2016","unstructured":"Crary JF (2016) Primary age-related tauopathy and the amyloid cascade hypothesis: the exception that proves the rule? J Neurol Neuromed 1:53\u201355. https:\/\/doi.org\/10.29245\/2572.942x\/2016\/6.1059","journal-title":"J Neurol Neuromed"},{"key":"2862_CR37","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1002\/alz.13737","volume":"20","author":"D Datta","year":"2024","unstructured":"Datta D, Perone I, Wijegunawardana D, Liang F, Morozov YM, Arellano J et al (2024) Nanoscale imaging of pT217-tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: evidence of interneuronal trafficking and early-stage neurodegeneration. Alzheimers Dement 20:2843\u20132860. https:\/\/doi.org\/10.1002\/alz.13737","journal-title":"Alzheimers Dement"},{"key":"2862_CR38","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.3233\/JAD-240483","volume":"101","author":"K Del Tredici","year":"2024","unstructured":"Del Tredici K, Sch\u00f6n M, Feldengut S, Ghebremedhin E, Kaufman SK, Wiesner D et al (2024) Early CA2 tau inclusions do not distinguish an age-related tauopathy from early Alzheimer\u2019s disease. J Alzheimers Dis 101:1333\u20131353. https:\/\/doi.org\/10.3233\/JAD-240483","journal-title":"J Alzheimers Dis"},{"key":"2862_CR39","doi-asserted-by":"publisher","first-page":"s006","DOI":"10.1007\/PL00007746","volume":"246","author":"DW Dickson","year":"1999","unstructured":"Dickson DW (1999) Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol 246:s006-s015. https:\/\/doi.org\/10.1007\/PL00007746","journal-title":"J Neurol"},{"key":"2862_CR40","first-page":"1","volume":"25","author":"DW Dickson","year":"2009","unstructured":"Dickson DW (2009) Neuropathology of non-Alzheimer degenerative disorders. Int J Clin Exp Pathol 25:1\u201323","journal-title":"Int J Clin Exp Pathol"},{"key":"2862_CR41","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1038\/s41591-020-0938-9","volume":"26","author":"S Dujardin","year":"2020","unstructured":"Dujardin S, Commins C, Lathuiliere A, Beerepoot P, Fernandes AR, Kamath TV et al (2020) Tau molecular diversity contributes to clinical heterogeneity in Alzheimer\u2019s disease. Nat Med 26:1256\u20131263. https:\/\/doi.org\/10.1038\/s41591-020-0938-9","journal-title":"Nat Med"},{"key":"2862_CR42","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/s0197-4580(97)00047-x","volume":"18","author":"C Duyckaerts","year":"1997","unstructured":"Duyckaerts C, Hauw JJ (1997) Prevalence, incidence and duration of Braak\u2019s stages in the general population: can we know? Neurobiol Aging 18:362\u2013369. https:\/\/doi.org\/10.1016\/s0197-4580(97)00047-x","journal-title":"Neurobiol Aging"},{"key":"2862_CR43","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00401-009-0532-1","volume":"118","author":"C Duyckaerts","year":"2009","unstructured":"Duyckaerts C, Delatour B, Potier MC (2009) Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118:5\u201336. https:\/\/doi.org\/10.1007\/s00401-009-0532-1","journal-title":"Acta Neuropathol"},{"key":"2862_CR44","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s00401-015-1390-7","volume":"129","author":"C Duyckaerts","year":"2015","unstructured":"Duyckaerts C, Braak H, Brion J-P, Bu\u00e9e L, Del Tredici K, Goedert M et al (2015) PART is part of Alzheimer disease. Acta Neuropathol 129:749\u2013756. https:\/\/doi.org\/10.1007\/s00401-015-1390-7","journal-title":"Acta Neuropathol"},{"key":"2862_CR45","first-page":"809","volume":"199","author":"C Duyckaerts","year":"2015","unstructured":"Duyckaerts C, Seilhean D, Sazdovitch V, Plu I, Delatour B, Potier MC (2015) Seeding and propagation of lesions in neurodegenerative diseases: a new paradigm. Bull Acad Natl Med 199:809\u2013819","journal-title":"Bull Acad Natl Med"},{"key":"2862_CR46","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1111\/nan.12387","volume":"43","author":"AJ Ehrenberg","year":"2017","unstructured":"Ehrenberg AJ, Nguy AK, Theophilas P, Dunlop S, Suemoto CK, Di Lorenzo Alho AT et al (2017) Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer\u2019s disease. Neurol Appl Neurobiol 43:393\u2013408. https:\/\/doi.org\/10.1111\/nan.12387","journal-title":"Neurol Appl Neurobiol"},{"key":"2862_CR47","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.jneumeth.2013.03.010","volume":"15","author":"S Feldengut","year":"2013","unstructured":"Feldengut S, Del Tredici K, Braak H (2013) Paraffin sections of 70\u2013100 \u00b5m: a novel technique and its benefits for studying the nervous system. J Neurosci Methods 15:241\u2013244. https:\/\/doi.org\/10.1016\/j.jneumeth.2013.03.010","journal-title":"J Neurosci Methods"},{"key":"2862_CR48","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/jama.1997.03550160069041","volume":"278","author":"LA Farrer","year":"1997","unstructured":"Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R et al (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278:1349\u20131356. https:\/\/doi.org\/10.1001\/jama.1997.03550160069041","journal-title":"JAMA"},{"key":"2862_CR49","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.13122","volume":"33","author":"I Ferrer","year":"2023","unstructured":"Ferrer I (2023) Hypothesis review: Alzheimer\u2019s overture guidelines. Brain Pathol 33:e13122. https:\/\/doi.org\/10.1111\/bpa.13122","journal-title":"Brain Pathol"},{"key":"2862_CR50","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.jalz.2007.08.005","volume":"4","author":"GG Fillenbaum","year":"2008","unstructured":"Fillenbaum GG, van Belle G, Morris JC, Mohs RC, Mirra SS, Davis PC et al (2008) Consortium to Establish a Registry for Alzheimer\u2019s Disease (CERAD): the first twenty years. Alzheimers Dement 4:96\u2013109. https:\/\/doi.org\/10.1016\/j.jalz.2007.08.005","journal-title":"Alzheimers Dement"},{"key":"2862_CR51","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/cne.903120111","volume":"312","author":"M Frotscher","year":"1991","unstructured":"Frotscher M, Seress L, Schwerdtfeger WK, Buhl E (1991) The mossy cells of the fascia dentata: a comparative study of their fine structure and synaptic connections in rodents and primates. J Comp Neurol 312:145\u2013163. https:\/\/doi.org\/10.1002\/cne.903120111","journal-title":"J Comp Neurol"},{"key":"2862_CR52","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s00441-006-0269-2","volume":"326","author":"M Frotscher","year":"2006","unstructured":"Frotscher M, Jonas P, Sloviter RS (2006) Synapses formed by normal and abnormal hippocampal mossy fibers. Cell Tiss Res 326:361\u2013367. https:\/\/doi.org\/10.1007\/s00441-006-0269-2","journal-title":"Cell Tiss Res"},{"key":"2862_CR53","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s00401-016-1644-z","volume":"133","author":"JL Furman","year":"2017","unstructured":"Furman JL, Vaquer-Alicea J, White CL, Cairns NJ, Nelson PT, Diamond MI (2017) Widespread tau seeding activity at early Braak stages. Acta Neuropathol 133:91\u2013100. https:\/\/doi.org\/10.1007\/s00401-016-1644-z","journal-title":"Acta Neuropathol"},{"key":"2862_CR54","first-page":"1","volume":"19","author":"F Gallyas","year":"1971","unstructured":"Gallyas F (1971) Silver staining of Alzheimer\u2019s neurofibrillary changes by means of physical development. Acta Morph Acad Sci Hung 19:1\u20138","journal-title":"Acta Morph Acad Sci Hung"},{"key":"2862_CR55","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/j.tins.2021.10.003","volume":"44","author":"S Genon","year":"2021","unstructured":"Genon S, Bernhardt BC, La Joie R, Amunts K, Eickhoff SB (2021) The many dimensions of human hippocampal (dys)function. Trends Neurosci 44:977\u2013989. https:\/\/doi.org\/10.1016\/j.tins.2021.10.003","journal-title":"Trends Neurosci"},{"key":"2862_CR56","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1006\/exnr.1998.6860","volume":"155","author":"E Ghebremedhin","year":"1998","unstructured":"Ghebremedhin E, Schultz C, Braak E, Braak H (1998) High frequency of apolipoprotein E \u03b54 allele in young individuals with very mild Alzheimer\u2019s disease-related neurofibrillary changes. Exp Neurol 155:152\u2013155. https:\/\/doi.org\/10.1006\/exnr.1998.6860","journal-title":"Exp Neurol"},{"key":"2862_CR57","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0304-3940(95)11484-e","volume":"189","author":"M Goedert","year":"1985","unstructured":"Goedert M, Jakes R, Vandermeeren E (1985) Monoclonal antibody AT8 recognizes tau protein phosphorylated at serine 202 and threonin 205. Neurosci Lett 189:167\u2013170. https:\/\/doi.org\/10.1016\/0304-3940(95)11484-e","journal-title":"Neurosci Lett"},{"key":"2862_CR58","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.tins.2010.04.003","volume":"33","author":"M Goedert","year":"2010","unstructured":"Goedert M, Clavaguera F, Tolnay M (2010) The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci 33:317\u2013325. https:\/\/doi.org\/10.1016\/j.tins.2010.04.003","journal-title":"Trends Neurosci"},{"key":"2862_CR59","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s11910-014-0495-z","volume":"14","author":"M Goedert","year":"2014","unstructured":"Goedert M, Falcon B, Clavaguera F, Tolnay M (2014) Prion-like mechanisms in the pathogenesis of tauopathies and synucleinopathies. Curr Neurol Neurosci Rep 14:495. https:\/\/doi.org\/10.1007\/s11910-014-0495-z","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2862_CR60","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s00429-023-02725-9","volume":"229","author":"E Gonz\u00e1lez-Arnay","year":"2024","unstructured":"Gonz\u00e1lez-Arnay E, P\u00e9rez-Santos I, Jim\u00e9nez-S\u00e1nchez L, Cid E, Gal B, de la Prida LM et al (2024) Immunohistochemical field parcellation of the human hippocampus along its antero-posterior axis. Brain Struct Funct 229:359\u2013385. https:\/\/doi.org\/10.1007\/s00429-023-02725-9","journal-title":"Brain Struct Funct"},{"key":"2862_CR61","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/0166-2236(92)90033-5","volume":"15","author":"J Hardy","year":"1992","unstructured":"Hardy J (1992) An \u2018anatomical cascade hypothesis\u2019 for Alzheimer\u2019s disease. Trends Neurosci 15:200\u2013201. https:\/\/doi.org\/10.1016\/0166-2236(92)90033-5","journal-title":"Trends Neurosci"},{"key":"2862_CR62","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s00401-018-1890-3","volume":"136","author":"H Heinsen","year":"2018","unstructured":"Heinsen H, Grinberg LT (2018) On the origin of tau seeding activity in Alzheimer\u2019s disease. Acta Neuropathol 136:815\u2013817. https:\/\/doi.org\/10.1007\/s00401-018-1890-3","journal-title":"Acta Neuropathol"},{"key":"2862_CR63","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/nn.4017","volume":"18","author":"K Herrup","year":"2015","unstructured":"Herrup K (2015) The case for rejecting the amyloid cascade hypothesis. Nat Neurosci 18:794\u2013799. https:\/\/doi.org\/10.1038\/nn.4017","journal-title":"Nat Neurosci"},{"key":"2862_CR64","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/BF00296179","volume":"87","author":"PR Hof","year":"1994","unstructured":"Hof PR, Bouras C, Perl P, Morrison JH (1994) Quantitative neuropathologic analysis of Pick\u2019s disease cases: cortical distribution of Pick bodies and coexistence with Alzheimer\u2019s disease. Acta Neuropathol 87:115\u2013124. https:\/\/doi.org\/10.1007\/BF00296179","journal-title":"Acta Neuropathol"},{"key":"2862_CR65","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1212\/wnl.40.11.1721","volume":"40","author":"BT Hyman","year":"1990","unstructured":"Hyman BT, van Hoesen GW, Damasio AR (1990) Memory-related systems in Alzheimer\u2019s disease: an anatomic study. Neurology 40:1721\u20131730. https:\/\/doi.org\/10.1212\/wnl.40.11.1721","journal-title":"Neurology"},{"key":"2862_CR66","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/0197-4580(94)90031-0","volume":"15","author":"BT Hyman","year":"1994","unstructured":"Hyman BT, Gom\u00e9z-Isla T (1994) Alzheimer\u2019s disease is a laminar, regional, and neural system specific disease, not a global brain disease. Neurobiol Aging 15:353\u2013354. https:\/\/doi.org\/10.1016\/0197-4580(94)90031-0","journal-title":"Neurobiol Aging"},{"key":"2862_CR67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","volume":"8","author":"BT Hyman","year":"2018","unstructured":"Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC et al (2018) 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":"2862_CR68","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/BF00304639","volume":"85","author":"K Ikeda","year":"1992","unstructured":"Ikeda K, Akiyama H, Haga C, Haga S (1992) Evidence that neurofibrillary tangles undergo glial modification. Acta Neuropathol 85:101\u2013104. https:\/\/doi.org\/10.1007\/BF00304639","journal-title":"Acta Neuropathol"},{"key":"2862_CR69","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/0304-3940(92)90820-w","volume":"148","author":"K Ikeda","year":"1992","unstructured":"Ikeda K, Haga C, Akiyama H, Kase K, Iritani S (1992) Coexistence of paired helical filaments and glial filaments in astrocytic processes within ghost tangles. Neurosci Lett 148:126\u2013128. https:\/\/doi.org\/10.1016\/0304-3940(92)90820-w","journal-title":"Neurosci Lett"},{"key":"2862_CR70","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/B978-0-12-374236-0.10024-0","volume-title":"The human nervous system","author":"R Insausti","year":"2012","unstructured":"Insausti R, Amaral DG (2012) Hippocampal formation. In: Mai JK, Paxinos G (eds) The human nervous system, 3rd edn. Academic Press, San Diego, pp 896\u2013942","edition":"3"},{"key":"2862_CR71","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00401-009-0486-3","volume":"118","author":"K Iqbal","year":"2009","unstructured":"Iqbal K, Liu F, Gong CX, Alonso C, Grundke-Iqbal I (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118:53\u201369. https:\/\/doi.org\/10.1007\/s00401-009-0486-3","journal-title":"Acta Neuropathol"},{"key":"2862_CR72","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.cell.2010.06.036","volume":"142","author":"LM Ittner","year":"2010","unstructured":"Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J et al (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer\u2019s disease mouse models. Cell 142:387\u2013397. https:\/\/doi.org\/10.1016\/j.cell.2010.06.036","journal-title":"Cell"},{"issue":"99","key":"2862_CR73","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.neuron.2018.06.003","volume":"11","author":"A Ittner","year":"2018","unstructured":"Ittner A, Ittner LM (2018) Dendritic tau in Alzheimer\u2018s disease. Neuron 11(99):13\u201327. https:\/\/doi.org\/10.1016\/j.neuron.2018.06.003","journal-title":"Neuron"},{"key":"2862_CR74","doi-asserted-by":"publisher","first-page":"eabj2511","DOI":"10.1126\/scitranslmed.abj2511","volume":"13","author":"HIL Jacobs","year":"2021","unstructured":"Jacobs HIL, Becker JA, Kwong K, Engels-Dom\u00ednguez N, Prokopiou PC, Papp KV et al (2021) In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer\u2019s disease pathology and cognitive decline. Sci Transl Med 13:eabj2511. https:\/\/doi.org\/10.1126\/scitranslmed.abj2511","journal-title":"Sci Transl Med"},{"key":"2862_CR75","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 (2018) Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer\u2018s disease. Front Neurosci 12:25. https:\/\/doi.org\/10.3389\/fnins.2018.00025","journal-title":"Front Neurosci"},{"key":"2862_CR76","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/jnc.13632","volume":"2","author":"E Karran","year":"2016","unstructured":"Karran E, De Strooper B (2016) The amyloid cascade hypothesis: are we poised for success or failure? J Neurochem 139. Suppl 2:237\u2013252. https:\/\/doi.org\/10.1111\/jnc.13632","journal-title":"Suppl"},{"key":"2862_CR77","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00401-018-1855-6","volume":"136","author":"SK Kaufman","year":"2018","unstructured":"Kaufman SK, Del Tredici K, Thomas TL, Braak H, Diamond MI (2018) Tau seeding activity begins in the transentorhinal\/entorhinal regions and anticipates phospho-tau pathology in Alzheimer\u2019s disease and PART. Acta Neuropathol 136:57\u201367. https:\/\/doi.org\/10.1007\/s00401-018-1855-6","journal-title":"Acta Neuropathol"},{"key":"2862_CR78","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2478\/s13380-012-0032-y","volume":"3","author":"KJ Kopelkina","year":"2012","unstructured":"Kopelkina KJ, Hyman BT, Spires-Jones TL (2012) Soluble forms of tau are toxic in Alzheimer\u2019s disease. Transl Neurosci 3:223\u2013233. https:\/\/doi.org\/10.2478\/s13380-012-0032-y","journal-title":"Transl Neurosci"},{"key":"2862_CR79","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00401-020-02158-2","volume":"140","author":"GG Kovacs","year":"2020","unstructured":"Kovacs GG, Lukic MJ, Irwin DJ, Arzberger T, Respondek G, Lee EB et al (2020) Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol 140:99\u2013119. https:\/\/doi.org\/10.1007\/s00401-020-02158-2","journal-title":"Acta Neuropathol"},{"key":"2862_CR80","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 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":"2862_CR81","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00401-015-1507-z","volume":"131","author":"J Lewis","year":"2016","unstructured":"Lewis J, Dickson DW (2016) Propagation of tau pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies. Acta Neuropathol 131:27\u201348. https:\/\/doi.org\/10.1007\/s00401-015-1507-z","journal-title":"Acta Neuropathol"},{"key":"2862_CR82","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1039\/d1cs00127b","volume":"51","author":"G Limorenko","year":"2022","unstructured":"Limorenko G, Lashuel HA (2022) Revisiting the grammar of tau aggregation and pathology formation: how new insights from brain pathology are shaping how we study and target tauopathies. Chem Soc Rev 51:563\u2013565. https:\/\/doi.org\/10.1039\/d1cs00127b","journal-title":"Chem Soc Rev"},{"key":"2862_CR83","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1212\/wnl.48.2.515","volume":"48","author":"CF Lippa","year":"1997","unstructured":"Lippa CF, Smith TW, Saunders AM, Hulette C, Pulaski-Salo D, Roses AD (1997) Apolipoprotein E-epsilon 2 and Alzheimer\u2018s disease: genotype influences pathologic phenotype. Neurology 48:515\u2013519. https:\/\/doi.org\/10.1212\/wnl.48.2.515","journal-title":"Neurology"},{"key":"2862_CR84","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","volume":"9","author":"CC Liu","year":"2013","unstructured":"Liu CC, Liu CC, Kanekiyo T et al (2013) Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 9:106\u2013118. https:\/\/doi.org\/10.1038\/nrneurol.2012.263. (Erratum.In:NatRevNeurol2013.10.1038\/nmeurol.2013.32.Liu,Chia-Chan[correctedtoLiu,Chia-Chen])","journal-title":"Nat Rev Neurol"},{"key":"2862_CR85","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102954","volume":"59","author":"AL Lumsden","year":"2020","unstructured":"Lumsden AL, Mulugeta A, Zhou A, Hypp\u00f6nen E (2020) Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK Biobank. EBioMedicine 59:102954. https:\/\/doi.org\/10.1016\/j.ebiom.2020.102954","journal-title":"EBioMedicine"},{"key":"2862_CR86","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1002\/cne.25466","volume":"531","author":"JJ Mahady","year":"2023","unstructured":"Mahady JJ, Perez SE, Malek-Ahmadi M, Mufson EJ (2023) Oligomeric, phosphorylated, and truncated tau and spliceosome pathology within the entorhinal-hippocampal connectome across stages of Alzheimer\u2019s disease. J Comp Neurol 531:2080\u20132108. https:\/\/doi.org\/10.1002\/cne.25466","journal-title":"J Comp Neurol"},{"key":"2862_CR87","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/prot.24988","volume":"84","author":"TJ Malia","year":"2016","unstructured":"Malia TJ, Teplyakov A, Ernst R, Wu SJ, Lacy ER, Liu X et al (2016) Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti-tau antibody AT8. Proteins 84:427\u2013434. https:\/\/doi.org\/10.1002\/prot.24988","journal-title":"Proteins"},{"key":"2862_CR88","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1093\/aje\/kwr015","volume":"173","author":"GJ McKay","year":"2011","unstructured":"McKay GJ, Silvestri G, Chakravarthy U, Dasari S, Fritsche LG, Weber BH et al (2011) Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people. Am J Epidemiol 173:1357\u20131364. https:\/\/doi.org\/10.1093\/aje\/kwr015","journal-title":"Am J Epidemiol"},{"key":"2862_CR89","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1093\/brain\/aws307","volume":"136","author":"AC McKee","year":"2013","unstructured":"McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH et al (2013) The spectrum of disease in chronic traumatic encephalopathy. Brain 136:43\u201364. https:\/\/doi.org\/10.1093\/brain\/aws307","journal-title":"Brain"},{"key":"2862_CR90","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1002\/acn3.581","volume":"5","author":"CT McMillan","year":"2018","unstructured":"McMillan CT, Lee EB, Jefferson-George K, Naj A, Van Deerlin VM, Trojanowski JQ et al (2018) Alzheimer\u2019s genetic risk is reduced in primary age-related tauopathy: a potential model of resistance? Ann Clin Transl Neurol 5:927\u2013934. https:\/\/doi.org\/10.1002\/acn3.581","journal-title":"Ann Clin Transl Neurol"},{"key":"2862_CR91","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1093\/brain\/awt088","volume":"136","author":"P Merino-Serrais","year":"2013","unstructured":"Merino-Serrais P, Benavides-Piccione R, Blazquez-Llorca L, Kastanauskaite A, Rabano A, Avila J et al (2013) The influence of phospho-\u03c4 on dendritic spines of cortical pyramidal neurons in patients with Alzheimer\u2019s disease. Brain 136:1913\u20131928. https:\/\/doi.org\/10.1093\/brain\/awt088","journal-title":"Brain"},{"key":"2862_CR92","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1159\/000365548","volume":"38","author":"I Milenkovic","year":"2014","unstructured":"Milenkovic I, Petrov T, Kovacs GG (2014) Patterns of hippocampal tau pathology differentiate neurodegenerative dementias. Dementia Geriatr Cogn Disord 38:375\u2013388. https:\/\/doi.org\/10.1159\/000365548","journal-title":"Dementia Geriatr Cogn Disord"},{"key":"2862_CR93","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1097\/00005072-199902000-00008","volume":"58","author":"R Morsch","year":"1999","unstructured":"Morsch R, Simon W, Coleman PD (1999) Neurons may live for decades with neurofibrillary tangles. J Neuropathol Exp Neurol 58:188\u2013197. https:\/\/doi.org\/10.1097\/00005072-199902000-00008","journal-title":"J Neuropathol Exp Neurol"},{"key":"2862_CR94","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s40478-017-0488-7","volume":"5","author":"A Mudher","year":"2017","unstructured":"Mudher A, Colin M, Dujardin S, Medina M, Dewachter I, Alavi Naini SM et al (2017) What is the evidence that tau pathology spreads through prion-like propagation? Acta Neuropathol Commun 5:99\u2013119. https:\/\/doi.org\/10.1186\/s40478-017-0488-7","journal-title":"Acta Neuropathol Commun"},{"key":"2862_CR95","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/0306-4522(95)90397-p","volume":"64","author":"TG Ohm","year":"1995","unstructured":"Ohm TG, M\u00fcller H, Braak H, Bohl J (1995) Close-meshed prevalence rates of different stages as a tool to unvover the rate of Alzheimer\u2019s disease-related neurofibrillary changes. Neurosci 64:209\u2013217. https:\/\/doi.org\/10.1016\/0306-4522(95)90397-p","journal-title":"Neurosci"},{"key":"2862_CR96","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/BF00707308","volume":"173","author":"HG Olbrich","year":"1985","unstructured":"Olbrich HG, Braak H (1985) Ratio of pyramidal cells versus non-pyramidal cells in sector CA1 of the human Ammon\u2019s horn. Anat Embryol 173:105\u2013110. https:\/\/doi.org\/10.1007\/BF00707308","journal-title":"Anat Embryol"},{"key":"2862_CR97","doi-asserted-by":"publisher","first-page":"e2127","DOI":"10.1212\/WNL.0000000000005677","volume":"90","author":"S Oveisgharan","year":"2018","unstructured":"Oveisgharan S, Buchman AS, Yu L, Farfel J, Hachinski V, Gaiteri C et al (2018) APOE \u03b52\u03b54 genotype, incident AD and MCI, cognitive decline, and AD pathology in older adults. Neurology 90:e2127\u2013e2134. https:\/\/doi.org\/10.1212\/WNL.0000000000005677","journal-title":"Neurology"},{"key":"2862_CR98","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1001\/jama.2020.12134","volume":"324","author":"S Palmqvist","year":"2020","unstructured":"Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E et al (2020) Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs. Other neurodegenerative disorders. JAMA 324:772\u2013781. https:\/\/doi.org\/10.1001\/jama.2020.12134","journal-title":"JAMA"},{"key":"2862_CR99","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/mds.20663","volume":"21","author":"N Pankratz","year":"2006","unstructured":"Pankratz N, Byder L, Halter C, Rudolph A, Shults CW, Conneally PM et al (2006) Presence of an APOE4 allele results in significantly earlier onset of Parkinson\u2019s disease and a higher risk with dementia. Mov Disord 21:45\u201349. https:\/\/doi.org\/10.1002\/mds.20663","journal-title":"Mov Disord"},{"key":"2862_CR100","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.3390\/jcm10081555","volume":"10","author":"A Patthy","year":"2021","unstructured":"Patthy A, Murai J, Hanics J, Pinter A, Zahola P, H\u00f6kfelt TGM et al (2021) Neuropathology of the brainstem to mechanistically understand and to treat Alzheimer\u00b4s disease. J Clin Med 10:1555\u20131578. https:\/\/doi.org\/10.3390\/jcm10081555","journal-title":"J Clin Med"},{"key":"2862_CR101","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1056\/NEJM199511093331902","volume":"333","author":"T Polvikoski","year":"1995","unstructured":"Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A et al (1995) Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. N Engl J Med 333:1242\u20131247. https:\/\/doi.org\/10.1056\/NEJM199511093331902","journal-title":"N Engl J Med"},{"key":"2862_CR102","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002254","volume":"14","author":"J Qian","year":"2017","unstructured":"Qian J, Wolters FJ, Beiser A et al (2017) APOE-related risk of mild cognitive impairment and dementia for prevention trials: an analysis of four cohorts. PLoS Med 14:e1002254. https:\/\/doi.org\/10.1371\/journal.pmed.1002254","journal-title":"PLoS Med"},{"key":"2862_CR103","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s13195-014-0082-1","volume":"6","author":"J Rahimi","year":"2014","unstructured":"Rahimi J, Kovacs GG (2014) Prevalence of mixed pathologies in the aging brain. Alzheimers Res Ther 6:82. https:\/\/doi.org\/10.1186\/s13195-014-0082-1","journal-title":"Alzheimers Res Ther"},{"key":"2862_CR104","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1186\/s13195-022-01074-9","volume":"14","author":"A Rubinski","year":"2022","unstructured":"Rubinski A, Franzmeier N, Dewenter A, Luan Y, Smith R, Strandberg O et al (2022) Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer\u2019s disease. Alzheimers Res Ther 14:139. https:\/\/doi.org\/10.1186\/s13195-022-01074-9","journal-title":"Alzheimers Res Ther"},{"key":"2862_CR105","doi-asserted-by":"publisher","first-page":"3893","DOI":"10.1016\/0306-4522(87)90063-7","volume":"23","author":"CB Saper","year":"1987","unstructured":"Saper CB, Wainer BH, German DC (1987) Axonal and transneuronal transport in the transmission of neurological disease: potential role in system degenerations, including Alzheimer\u2019s disease. Neuroscience 23:3893\u20133898. https:\/\/doi.org\/10.1016\/0306-4522(87)90063-7","journal-title":"Neuroscience"},{"key":"2862_CR106","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s00441-017-2750-5","volume":"373","author":"HE Scharfman","year":"2018","unstructured":"Scharfman HE (2018) Advances in understanding hilar mossy cells of the dentate gyrus. Cell Tiss Res 373:643\u2013652. https:\/\/doi.org\/10.1007\/s00441-017-2750-5","journal-title":"Cell Tiss Res"},{"key":"2862_CR107","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.neurobiolaging.2003.09.009","volume":"25","author":"B Sch\u00f6nheit","year":"2004","unstructured":"Sch\u00f6nheit B, Zarski R, Ohm TG (2004) Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol Aging 25:697\u2013711. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2003.09.009","journal-title":"Neurobiol Aging"},{"key":"2862_CR108","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/0896-6273(91)90052-2","volume":"6","author":"DJ Selkoe","year":"1991","unstructured":"Selkoe DJ (1991) The molecular pathology of Alzheimer\u2019s disease. Neuron 6:487\u2013498. https:\/\/doi.org\/10.1016\/0896-6273(91)90052-2","journal-title":"Neuron"},{"key":"2862_CR109","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nature24016","volume":"549","author":"Y Shi","year":"2017","unstructured":"Shi Y, Yamada K, Liddelow SA, Smith ST, Zhao L, Luo W et al (2017) ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549:523\u2013527. https:\/\/doi.org\/10.1038\/nature24016","journal-title":"Nature"},{"key":"2862_CR110","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/S1474-4422(13)70090-5","volume":"12","author":"MG Spillantini","year":"2013","unstructured":"Spillantini MG, Goedert M (2013) Tau pathology and neurodegeneration. Lancet Neurol 12:609\u2013622. https:\/\/doi.org\/10.1016\/S1474-4422(13)70090-5","journal-title":"Lancet Neurol"},{"key":"2862_CR111","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1111\/bpa.12289","volume":"26","author":"K Stratmann","year":"2016","unstructured":"Stratmann K, Heinsen H, Korf HW, Del Turco D, Ghebremedhin E, Seidel K et al (2016) Precortical phase of Alzheimer\u2019s disease (AD)-related tau cytoskeletal pathology. Brain Pathol 26:371\u2013386. https:\/\/doi.org\/10.1111\/bpa.12289","journal-title":"Brain Pathol"},{"key":"2862_CR112","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.neuroimage.2008.11.027","volume":"45","author":"NH Stricker","year":"2009","unstructured":"Stricker NH, Schweinsburg BC, Delano-Wood L, Wierenga CE, Bangen KJ, Haaland KY et al (2009) Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer\u2019s disease supports retrogenesis. Neuroimage 45:10\u201316. https:\/\/doi.org\/10.1016\/j.neuroimage.2008.11.027","journal-title":"Neuroimage"},{"key":"2862_CR113","doi-asserted-by":"publisher","first-page":"14263","DOI":"10.1016\/j.ajpath.2012.06.033","volume":"181","author":"HC Tai","year":"2012","unstructured":"Tai HC, Serrano-Pozo A, Hashimoto T, Frosch M, Spires-Jones TL, Hyman BT (2012) The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system. Am J Pathol 181:14263\u201314265. https:\/\/doi.org\/10.1016\/j.ajpath.2012.06.033. (Erratum.In:AmJPathol2012;181:1889-1890)","journal-title":"Am J Pathol"},{"key":"2862_CR114","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.1097\/00001756-199708180-00029","volume":"8","author":"K Tashiro","year":"1997","unstructured":"Tashiro K, Hasegawa M, Ihara Y, Iwatsubo T (1997) Somatodendritic localization of phosphorylated tau in neonatal and adult rat cerebral cortex. NeuroReport 8:2797\u20132801. https:\/\/doi.org\/10.1097\/00001756-199708180-00029","journal-title":"NeuroReport"},{"key":"2862_CR115","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1016\/j.neurobiolaging.2007.03.024","volume":"29","author":"KI Taylor","year":"2008","unstructured":"Taylor KI, Probst A (2008) Anatomic localization of the transentorhinal region of the perirhinal cortex. Neurobiol Aging 29:1591\u20131596. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2007.03.024","journal-title":"Neurobiol Aging"},{"key":"2862_CR116","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1038\/s43587-022-00204-0","volume":"2","author":"J Therriault","year":"2022","unstructured":"Therriault J, Pascoal TA, Lussier FZ, Tissot C, Chamoun M, Bezgin G et al (2022) Biomarker modeling of Alzheimer\u2019s disease using PET-based Braak staging. Nat Aging 2:526\u2013535. https:\/\/doi.org\/10.1038\/s43587-022-00204-0","journal-title":"Nat Aging"},{"key":"2862_CR117","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1212\/01.wnl.0000128091.92139.0f","volume":"62","author":"P Tiraboschi","year":"2004","unstructured":"Tiraboschi P, Hansen LA, Masliah E, Alford M, Thal LJ, Corey-Bloom J (2004) Impact of APOE genotype on neuropathologic and neurochemical markers of Alzheimer disease. Neurology 62:1977\u20131983. https:\/\/doi.org\/10.1212\/01.wnl.0000128091.92139.0f","journal-title":"Neurology"},{"key":"2862_CR118","doi-asserted-by":"publisher","first-page":"84","DOI":"10.2174\/156720510790274482","volume":"1","author":"IK Tsamis","year":"2020","unstructured":"Tsamis IK, Mytillinaios GD, Njau NS, Toiou FD, Glaftsi S, Costa V et al (2020) Properties of CA3 dendritic excrescences in Alzheimer\u2019s disease. Curr Alzheimer Res 1:84\u201390. https:\/\/doi.org\/10.2174\/156720510790274482","journal-title":"Curr Alzheimer Res"},{"key":"2862_CR119","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1001\/jamaneurol.2013.600","volume":"70","author":"D Tsuang","year":"2013","unstructured":"Tsuang D, Leverenz JB, Lopez OL, Hamilton RL, Bennett DA, Schneider JA et al (2013) APOE \u03b54 increases risk for dementia in pure synucleinopathies. JAMA Neurol 70:223\u2013228. https:\/\/doi.org\/10.1001\/jamaneurol.2013.600","journal-title":"JAMA Neurol"},{"key":"2862_CR120","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s004010000306","volume":"101","author":"T Uchihara","year":"2001","unstructured":"Uchihara T, Nakamura A, Yamazaki M, Mori O (2001) Evolution from pretangle neurons to neurofibrillary tangles monitored by thiazin red combined with Gallyas method and double immunofluorescence. Acta Neuropathol 101:535\u2013539. https:\/\/doi.org\/10.1007\/s004010000306","journal-title":"Acta Neuropathol"},{"key":"2862_CR121","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.conb.2018.04.013","volume":"52","author":"M Valero","year":"2018","unstructured":"Valero M, Menendez de la Prida L (2018) The hippocampus in depth: a sublayer-specific perspective of entorhinal-hippocampal function. Curr Opin Neurobiol 52:107\u2013114. https:\/\/doi.org\/10.1016\/j.conb.2018.04.013","journal-title":"Curr Opin Neurobiol"},{"key":"2862_CR122","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":"2862_CR123","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/s0006-8993(98)01034-8","volume":"813","author":"ME Velasco","year":"1998","unstructured":"Velasco ME, Smith MA, Siedlak SI, Nunomura A, Perry G (1998) Striation is the characteristic neuritic abnormality in Alzheimer disease. Brain Res 813:329\u2013333. https:\/\/doi.org\/10.1016\/s0006-8993(98)01034-8","journal-title":"Brain Res"},{"key":"2862_CR124","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.biopsych.2019.09.019","volume":"87","author":"T Vogels","year":"2020","unstructured":"Vogels T, Lenzy A, Cicognolla C, Ashton NJ, Smolek T, Novak M et al (2020) Propagation of tau pathology: insights from postmortem an in vivo studies. Biol Psychiatry 87:808\u2013818. https:\/\/doi.org\/10.1016\/j.biopsych.2019.09.019","journal-title":"Biol Psychiatry"},{"key":"2862_CR125","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000334607","volume":"38","author":"A Ward","year":"2012","unstructured":"Ward A, Crean S, Mercaldi CJ, Collins JM, Boyd D, Cook MN et al (2012) Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4\/4) among patients diagnosed with Alzheimer\u2019s disease: a systematic review and metaanalysis. Neuroepidemiology 38:1\u201317. https:\/\/doi.org\/10.1159\/000334607","journal-title":"Neuroepidemiology"},{"key":"2862_CR126","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1001\/jamaneurol.2018.3139","volume":"75","author":"AM Wenneberg","year":"2018","unstructured":"Wenneberg AM, Tosakulwong N, Lesnick TG, Murray ME, Whitwell JL, Liesinger AM et al (2018) Association of apolipoprotein E \u03b54 with transactive response DNA-binding protein 43. JAMA Neurol 75:1347\u20131354. https:\/\/doi.org\/10.1001\/jamaneurol.2018.3139","journal-title":"JAMA Neurol"},{"key":"2862_CR127","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0079-6123(07)63003-9","volume":"163","author":"MP Witter","year":"2007","unstructured":"Witter MP (2007) The perforant path: projections from the entorhinal cortex to the dentate gyrus. Prog Brain Res 163:43\u201361. https:\/\/doi.org\/10.1016\/S0079-6123(07)63003-9","journal-title":"Prog Brain Res"},{"key":"2862_CR128","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s40478-020-00967-w","volume":"8","author":"Y Xia","year":"2020","unstructured":"Xia Y, Prokop S, Gorion KM, Kim JD, Sorrentino ZA, Bell BM et al (2020) Tau Ser208 phosphorylation promotes aggregation and reveals neuropathologic diversity in Alzheimer\u2019s disease and other tauopathies. Acta Neuropathol Commun 8:88. https:\/\/doi.org\/10.1186\/s40478-020-00967-w","journal-title":"Acta Neuropathol Commun"},{"key":"2862_CR129","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1007\/s12031-020-01573-0","volume":"70","author":"L Zhang","year":"2020","unstructured":"Zhang L, Jiang Y, Zhu J, Liang H, He X, Qian J et al (2020) Quantitative assessment of hippocampal tau pathology in AD and PART. J Mol Neurosci 70:1808\u20131811. https:\/\/doi.org\/10.1007\/s12031-020-01573-0","journal-title":"J Mol Neurosci"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02862-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-025-02862-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02862-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T15:17:51Z","timestamp":1757171871000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-025-02862-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,23]]},"references-count":129,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["2862"],"URL":"https:\/\/doi.org\/10.1007\/s00401-025-02862-x","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,23]]},"assertion":[{"value":"19 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no current or potential conflicts of interest to report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"50"}}