{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:10:50Z","timestamp":1792782650103,"version":"4.5.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH\/NIA","award":["R01AG091577"],"award-info":[{"award-number":["R01AG091577"]}]},{"name":"CureAlz Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The aggregation of the microtubule-associated protein tau into oligomeric complexes is strongly correlated with the onset and progression of neurodegeneration in Alzheimer\u2019s disease (AD). Increasing evidence implicates nuclear membrane disruption in AD and related tauopathies; however, whether this is a cause or consequence of neurodegeneration remains unresolved. Here, we show that nuclear lamina disruption emerges at the early Braak stages, coinciding with the initial formation of pathological tau aggregates in post-mortem AD brain tissue. Using the tauopathy mouse model (P301S PS19), we demonstrate that oligomeric tau (oTau) directly binds to the Lamin B Receptor (LBR), inducing nuclear envelope invaginations as revealed by electron microscopy. These structural alterations are accompanied by chromatin remodeling and gene expression dysregulation. To dissect the underlying mechanism, we employed a light-inducible OptoTau system (4R1N Tau::mCherry::Cry2Olig) in human iPSC-derived neurons, enabling real-time visualization of tau aggregation dynamics. This system revealed selective recruitment of oTau to the nuclear envelope and direct interactions with LBR and Lamin B2, leading to nuclear deformation and activation of the protein translational stress response. Together, these findings identify nuclear membrane disruption as an early and potentially causative event in tau-mediated neurodegeneration, establishing a mechanistic link between tau oligomerization, nuclear stress, and chromatin remodeling. Targeting nuclear destabilization may offer new therapeutic avenues for mitigating AD pathogenesis.<\/jats:p>","DOI":"10.1007\/s00401-026-03018-1","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T08:36:45Z","timestamp":1776847005000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tau oligomerization induces nuclear lamina invagination and chromatin remodeling in Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"151","author":[{"given":"Shuo","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Essepian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Sherman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika M.","family":"Gniadzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alev","family":"Erisir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"3018_CR1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/s0197-4580(00)00124-x","volume":"21","author":"H Akiyama","year":"2000","unstructured":"Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM et al (2000) Inflammation and Alzheimer\u2019s disease. Neurobiol Aging 21:383\u2013421. https:\/\/doi.org\/10.1016\/s0197-4580(00)00124-x","journal-title":"Neurobiol Aging"},{"key":"3018_CR2","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1212\/wnl.42.3.631","volume":"42","author":"PV Arriagada","year":"1992","unstructured":"Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer\u2019s disease. Neurology 42:631\u2013639. https:\/\/doi.org\/10.1212\/wnl.42.3.631","journal-title":"Neurology"},{"key":"3018_CR3","doi-asserted-by":"publisher","first-page":"4466","DOI":"10.1038\/s41467-023-40208-x","volume":"14","author":"M Askenazi","year":"2023","unstructured":"Askenazi M, Kavanagh T, Pires G, Ueberheide B, Wisniewski T, Drummond E (2023) Compilation of reported protein changes in the brain in Alzheimer\u2019s disease. Nat Commun 14:4466. https:\/\/doi.org\/10.1038\/s41467-023-40208-x","journal-title":"Nat Commun"},{"key":"3018_CR4","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/nrn2194","volume":"8","author":"C Ballatore","year":"2007","unstructured":"Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer\u2019s disease and related disorders. Nat Rev Neurosci 8:663\u2013672. https:\/\/doi.org\/10.1038\/nrn2194","journal-title":"Nat Rev Neurosci"},{"key":"3018_CR5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200861","author":"NR Barth\u00e9lemy","year":"2020","unstructured":"Barth\u00e9lemy NR, Horie K, Sato C, Bateman RJ (2020) Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer\u2019s disease. J Exp Med. https:\/\/doi.org\/10.1084\/jem.20200861","journal-title":"J Exp Med"},{"key":"3018_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14403","author":"S Buchholz","year":"2025","unstructured":"Buchholz S, Kabbani MAA, Bell-Simons M, Kluge L, Cagmak C, Klimek J et al (2025) The tau isoform 1N4R confers vulnerability of MAPT knockout human iPSC-derived neurons to amyloid beta and phosphorylated tau-induced neuronal dysfunction. Alzheimers Dement. https:\/\/doi.org\/10.1002\/alz.14403","journal-title":"Alzheimers Dement"},{"key":"3018_CR7","doi-asserted-by":"publisher","first-page":"12879","DOI":"10.1073\/pnas.0506001102","volume":"102","author":"BC Capell","year":"2005","unstructured":"Capell BC, Erdos MR, Madigan JP, Fiordalisi JJ, Varga R, Conneely KN et al (2005) Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A 102:12879\u201312884. https:\/\/doi.org\/10.1073\/pnas.0506001102","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3018_CR8","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1091\/mbc.E10-07-0654","volume":"22","author":"KH Chang","year":"2011","unstructured":"Chang KH, Multani PS, Sun KH, Vincent F, de Pablo Y, Ghosh S et al (2011) Nuclear envelope dispersion triggered by deregulated Cdk5 precedes neuronal death. Mol Biol Cell 22:1452\u20131462. https:\/\/doi.org\/10.1091\/mbc.E10-07-0654","journal-title":"Mol Biol Cell"},{"key":"3018_CR9","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12974-023-02853-3","volume":"20","author":"Y Chen","year":"2023","unstructured":"Chen Y, Yu Y (2023) Tau and neuroinflammation in Alzheimer\u2019s disease: interplay mechanisms and clinical translation. J Neuroinflammation 20:165. https:\/\/doi.org\/10.1186\/s12974-023-02853-3","journal-title":"J Neuroinflammation"},{"key":"3018_CR10","doi-asserted-by":"publisher","first-page":"4683","DOI":"10.1091\/mbc.E11-06-0504","volume":"22","author":"C Coffinier","year":"2011","unstructured":"Coffinier C, Jung HJ, Nobumori C, Chang S, Tu Y, Barnes RH et al (2011) Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons. Mol Biol Cell 22:4683\u20134693. https:\/\/doi.org\/10.1091\/mbc.E11-06-0504","journal-title":"Mol Biol Cell"},{"key":"3018_CR11","volume-title":"The cell: a molecular approach","author":"GM Cooper","year":"2000","unstructured":"Cooper GM (2000) The cell: a molecular approach. ASM Press, City"},{"key":"3018_CR12","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nrneurol.2012.156","volume":"8","author":"J Cooper-Knock","year":"2012","unstructured":"Cooper-Knock J, Kirby J, Ferraiuolo L, Heath PR, Rattray M, Shaw PJ (2012) Gene expression profiling in human neurodegenerative disease. Nat Rev Neurol 8:518\u2013530. https:\/\/doi.org\/10.1038\/nrneurol.2012.156","journal-title":"Nat Rev Neurol"},{"key":"3018_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00114","volume":"4","author":"CM Cowan","year":"2013","unstructured":"Cowan CM, Mudher A (2013) Are tau aggregates toxic or protective in tauopathies? Front Neurol 4:114. https:\/\/doi.org\/10.3389\/fneur.2013.00114","journal-title":"Front Neurol"},{"key":"3018_CR14","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1042\/BST20120135","volume":"40","author":"CM Cowan","year":"2012","unstructured":"Cowan CM, Quraishe S, Mudher A (2012) What is the pathological significance of tau oligomers? Biochem Soc Trans 40:693\u2013697. https:\/\/doi.org\/10.1042\/BST20120135","journal-title":"Biochem Soc Trans"},{"key":"3018_CR15","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1101\/gad.1652708","volume":"22","author":"T Dechat","year":"2008","unstructured":"Dechat T, Pfleghaar K, Sengupta K, Shimi T, Shumaker DK, Solimando L et al (2008) Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22:832\u2013853. https:\/\/doi.org\/10.1101\/gad.1652708","journal-title":"Genes Dev"},{"key":"3018_CR16","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.neuron.2018.07.039","volume":"99","author":"B Eftekharzadeh","year":"2018","unstructured":"Eftekharzadeh B, Daigle JG, Kapinos LE, Coyne A, Schiantarelli J, Carlomagno Y et al (2018) Tau protein disrupts nucleocytoplasmic transport in Alzheimer\u2019s disease. Neuron 99:925-940.e927. https:\/\/doi.org\/10.1016\/j.neuron.2018.07.039","journal-title":"Neuron"},{"key":"3018_CR17","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.neuron.2018.12.031","volume":"101","author":"B Eftekharzadeh","year":"2019","unstructured":"Eftekharzadeh B, Daigle JG, Kapinos LE, Coyne A, Schiantarelli J, Carlomagno Y et al (2019) Tau protein disrupts nucleocytoplasmic transport in Alzheimer\u2019s disease. Neuron 101:349","journal-title":"Neuron"},{"key":"3018_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2024.1456052","volume":"17","author":"RMA Fisher","year":"2024","unstructured":"Fisher RMA, Torrente MP (2024) Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics. Front Mol Neurosci 17:1456052. https:\/\/doi.org\/10.3389\/fnmol.2024.1456052","journal-title":"Front Mol Neurosci"},{"key":"3018_CR19","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.tins.2023.07.006","volume":"46","author":"B Frost","year":"2023","unstructured":"Frost B (2023) Alzheimer\u2019s disease and related tauopathies: disorders of disrupted neuronal identity. Trends Neurosci 46:797\u2013813. https:\/\/doi.org\/10.1016\/j.tins.2023.07.006","journal-title":"Trends Neurosci"},{"key":"3018_CR20","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.cub.2015.11.039","volume":"26","author":"B Frost","year":"2016","unstructured":"Frost B, Bardai FH, Feany MB (2016) Lamin dysfunction mediates neurodegeneration in tauopathies. Curr Biol 26:129\u2013136. https:\/\/doi.org\/10.1016\/j.cub.2015.11.039","journal-title":"Curr Biol"},{"key":"3018_CR21","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nn.3639","volume":"17","author":"B Frost","year":"2014","unstructured":"Frost B, Hemberg M, Lewis J, Feany MB (2014) Tau promotes neurodegeneration through global chromatin relaxation. Nat Neurosci 17:357\u2013366. https:\/\/doi.org\/10.1038\/nn.3639","journal-title":"Nat Neurosci"},{"key":"3018_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00093","volume":"4","author":"JE Gerson","year":"2013","unstructured":"Gerson JE, Kayed R (2013) Formation and propagation of tau oligomeric seeds. Front Neurol 4:93. https:\/\/doi.org\/10.3389\/fneur.2013.00093","journal-title":"Front Neurol"},{"key":"3018_CR23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910283","author":"L Gil","year":"2021","unstructured":"Gil L, Nino SA, Guerrero C, Jimenez-Capdeville ME (2021) Phospho-tau and chromatin landscapes in early and late Alzheimer\u2019s disease. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms221910283","journal-title":"Int J Mol Sci"},{"key":"3018_CR24","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.bbadis.2004.08.007","volume":"1739","author":"M Goedert","year":"2005","unstructured":"Goedert M, Jakes R (2005) Mutations causing neurodegenerative tauopathies. Biochim Biophys Acta 1739:240\u2013250. https:\/\/doi.org\/10.1016\/j.bbadis.2004.08.007","journal-title":"Biochim Biophys Acta"},{"key":"3018_CR25","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s00702-004-0221-0","volume":"112","author":"CX Gong","year":"2005","unstructured":"Gong CX, Liu F, Grundke-Iqbal I, Iqbal K (2005) Post-translational modifications of tau protein in Alzheimer\u2019s disease. J Neural Transm (Vienna) 112:813\u2013838. https:\/\/doi.org\/10.1007\/s00702-004-0221-0","journal-title":"J Neural Transm (Vienna)"},{"key":"3018_CR26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.arr.2016.06.007","volume":"33","author":"S Gonzalo","year":"2017","unstructured":"Gonzalo S, Kreienkamp R, Askjaer P (2017) Hutchinson-Gilford progeria syndrome: a premature aging disease caused by LMNA gene mutations. Ageing Res Rev 33:18\u201329. https:\/\/doi.org\/10.1016\/j.arr.2016.06.007","journal-title":"Ageing Res Rev"},{"key":"3018_CR27","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1111\/j.1582-4934.2008.00402.x","volume":"12","author":"AM Gorman","year":"2008","unstructured":"Gorman AM (2008) Neuronal cell death in neurodegenerative diseases: recurring themes around protein handling. J Cell Mol Med 12:2263\u20132280. https:\/\/doi.org\/10.1111\/j.1582-4934.2008.00402.x","journal-title":"J Cell Mol Med"},{"key":"3018_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.04.020","author":"SI Graves","year":"2025","unstructured":"Graves SI, Meyer CF, Jeganathan KB, Baker DJ (2025) p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice. Neuron. https:\/\/doi.org\/10.1016\/j.neuron.2025.04.020","journal-title":"Neuron"},{"key":"3018_CR29","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000539","volume":"2","author":"MW Hetzer","year":"2010","unstructured":"Hetzer MW (2010) The nuclear envelope. Cold Spring Harb Perspect Biol 2:a000539. https:\/\/doi.org\/10.1101\/cshperspect.a000539","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"3018_CR30","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s00401-015-1458-4","volume":"130","author":"M Iba","year":"2015","unstructured":"Iba M, McBride JD, Guo JL, Zhang B, Trojanowski JQ, Lee VM (2015) Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC\u2019s afferent and efferent connections. Acta Neuropathol 130:349\u2013362. https:\/\/doi.org\/10.1007\/s00401-015-1458-4","journal-title":"Acta Neuropathol"},{"key":"3018_CR31","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature10821","volume":"482","author":"MA Israel","year":"2012","unstructured":"Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C et al (2012) Probing sporadic and familial Alzheimer\u2019s disease using induced pluripotent stem cells. Nature 482:216\u2013220. https:\/\/doi.org\/10.1038\/nature10821","journal-title":"Nature"},{"key":"3018_CR32","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1038\/s41467-020-15436-0","volume":"11","author":"S Janelidze","year":"2020","unstructured":"Janelidze S, Stomrud E, Smith R, Palmqvist S, Mattsson N, Airey DC et al (2020) Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer\u2019s disease. Nat Commun 11:1683. https:\/\/doi.org\/10.1038\/s41467-020-15436-0","journal-title":"Nat Commun"},{"key":"3018_CR33","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00401-018-1937-5","volume":"137","author":"L Jiang","year":"2019","unstructured":"Jiang L, Ash PEA, Maziuk BF, Ballance HI, Boudeau S, Abdullatif AA et al (2019) TIA1 regulates the generation and response to toxic tau oligomers. Acta Neuropathol 137:259\u2013277. https:\/\/doi.org\/10.1007\/s00401-018-1937-5","journal-title":"Acta Neuropathol"},{"key":"3018_CR34","doi-asserted-by":"publisher","first-page":"4209","DOI":"10.1016\/j.molcel.2021.07.038","volume":"81","author":"L Jiang","year":"2021","unstructured":"Jiang L, Lin W, Zhang C, Ash PEA, Verma M, Kwan J et al (2021) Interaction of tau with HNRNPA2B1 and N. Mol Cell 81:4209-4227.e4212. https:\/\/doi.org\/10.1016\/j.molcel.2021.07.038","journal-title":"Mol Cell"},{"key":"3018_CR35","doi-asserted-by":"publisher","DOI":"10.1002\/alz.054521","volume":"17","author":"L Jiang","year":"2021","unstructured":"Jiang L, Wolozin B (2021) Oligomeric tau disrupts nuclear envelope via binding to lamin proteins and lamin B receptor. Alzheimers Dement 17:e054521. https:\/\/doi.org\/10.1002\/alz.054521","journal-title":"Alzheimers Dement"},{"key":"3018_CR36","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1046\/j.1471-4159.1997.69052087.x","volume":"69","author":"GA Jicha","year":"1997","unstructured":"Jicha GA, Lane E, Vincent I, Otvos L, Hoffmann R, Davies P (1997) A conformation- and phosphorylation-dependent antibody recognizing the paired helical filaments of Alzheimer\u2019s disease. J Neurochem 69:2087\u20132095. https:\/\/doi.org\/10.1046\/j.1471-4159.1997.69052087.x","journal-title":"J Neurochem"},{"key":"3018_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-2-18","volume":"2","author":"R Kayed","year":"2007","unstructured":"Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M et al (2007) Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener 2:18. https:\/\/doi.org\/10.1186\/1750-1326-2-18","journal-title":"Mol Neurodegener"},{"key":"3018_CR38","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/jnr.10328","volume":"69","author":"MD Kirkitadze","year":"2002","unstructured":"Kirkitadze MD, Bitan G, Teplow DB (2002) Paradigm shifts in Alzheimer\u2019s disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies. J Neurosci Res 69:567\u2013577. https:\/\/doi.org\/10.1002\/jnr.10328","journal-title":"J Neurosci Res"},{"key":"3018_CR39","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41593-018-0291-1","volume":"22","author":"HU Klein","year":"2019","unstructured":"Klein HU, McCabe C, Gjoneska E, Sullivan SE, Kaskow BJ, Tang A et al (2019) Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer\u2019s human brains. Nat Neurosci 22:37\u201346. https:\/\/doi.org\/10.1038\/s41593-018-0291-1","journal-title":"Nat Neurosci"},{"key":"3018_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00269-y","volume":"7","author":"DS Knopman","year":"2021","unstructured":"Knopman DS, Amieva H, Petersen RC, Chetelat G, Holtzman DM, Hyman BT et al (2021) Alzheimer disease. Nat Rev Dis Primers 7:33. https:\/\/doi.org\/10.1038\/s41572-021-00269-y","journal-title":"Nat Rev Dis Primers"},{"key":"3018_CR41","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.stem.2013.01.009","volume":"12","author":"T Kondo","year":"2013","unstructured":"Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y et al (2013) Modeling Alzheimer\u2019s disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness. Cell Stem Cell 12:487\u2013496. https:\/\/doi.org\/10.1016\/j.stem.2013.01.009","journal-title":"Cell Stem Cell"},{"key":"3018_CR42","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202307142","author":"G Korsten","year":"2024","unstructured":"Korsten G, Osinga M, Pelle RA, Serweta AK, Hoogenberg B, Kampinga HH et al (2024) Nuclear poly-glutamine aggregates rupture the nuclear envelope and hinder its repair. J Cell Biol. https:\/\/doi.org\/10.1083\/jcb.202307142","journal-title":"J Cell Biol"},{"key":"3018_CR43","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1263310","volume":"17","author":"FD Koufi","year":"2023","unstructured":"Koufi FD, Neri I, Ramazzotti G, Rusciano I, Mongiorgi S, Marvi MV et al (2023) Lamin B1 as a key modulator of the developing and aging brain. Front Cell Neurosci 17:1263310. https:\/\/doi.org\/10.3389\/fncel.2023.1263310","journal-title":"Front Cell Neurosci"},{"key":"3018_CR44","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030718","author":"L Kristiani","year":"2020","unstructured":"Kristiani L, Kim M, Kim Y (2020) Role of the nuclear lamina in age-associated nuclear reorganization and inflammation. Cells. https:\/\/doi.org\/10.3390\/cells9030718","journal-title":"Cells"},{"key":"3018_CR45","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1093\/brain\/awad378","volume":"147","author":"M Kumar","year":"2024","unstructured":"Kumar M, Quittot N, Dujardin S, Schlaffner CN, Viode A, Wiedmer A et al (2024) Alzheimer proteopathic tau seeds are biochemically a forme fruste of mature paired helical filaments. Brain 147:637\u2013648. https:\/\/doi.org\/10.1093\/brain\/awad378","journal-title":"Brain"},{"key":"3018_CR46","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-6-39","volume":"6","author":"CA Lasagna-Reeves","year":"2011","unstructured":"Lasagna-Reeves CA, Castillo-Carranza DL, Sengupta U, Clos AL, Jackson GR, Kayed R (2011) Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice. Mol Neurodegener 6:39. https:\/\/doi.org\/10.1186\/1750-1326-6-39","journal-title":"Mol Neurodegener"},{"key":"3018_CR47","doi-asserted-by":"publisher","first-page":"3532","DOI":"10.1093\/bioinformatics\/btw413","volume":"32","author":"D Legland","year":"2016","unstructured":"Legland D, Arganda-Carreras I, Andrey P (2016) MorphoLibJ: integrated library and plugins for mathematical morphology with ImageJ. Bioinformatics 32:3532\u20133534. https:\/\/doi.org\/10.1093\/bioinformatics\/btw413","journal-title":"Bioinformatics"},{"key":"3018_CR48","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1016\/j.neuron.2021.03.026","volume":"109","author":"E Lester","year":"2021","unstructured":"Lester E, Ooi FK, Bakkar N, Ayers J, Woerman AL, Wheeler J et al (2021) Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components. Neuron 109:1675-1691 e1679. https:\/\/doi.org\/10.1016\/j.neuron.2021.03.026","journal-title":"Neuron"},{"key":"3018_CR49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217759120","volume":"120","author":"E Lester","year":"2023","unstructured":"Lester E, Van Alstyne M, McCann KL, Reddy S, Cheng LY, Kuo J et al (2023) Cytosolic condensates rich in polyserine define subcellular sites of tau aggregation. Proc Natl Acad Sci USA 120:e2217759120. https:\/\/doi.org\/10.1073\/pnas.2217759120","journal-title":"Proc Natl Acad Sci USA"},{"key":"3018_CR50","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006247","volume":"2","author":"EM Mandelkow","year":"2012","unstructured":"Mandelkow EM, Mandelkow E (2012) Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med 2:a006247. https:\/\/doi.org\/10.1101\/cshperspect.a006247","journal-title":"Cold Spring Harb Perspect Med"},{"key":"3018_CR51","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13035","volume":"18","author":"M Montalbano","year":"2019","unstructured":"Montalbano M, McAllen S, Sengupta U, Puangmalai N, Bhatt N, Ellsworth A et al (2019) Tau oligomers mediate aggregation of RNA-binding proteins Musashi1 and Musashi2 inducing Lamin alteration. Aging Cell 18:e13035. https:\/\/doi.org\/10.1111\/acel.13035","journal-title":"Aging Cell"},{"key":"3018_CR52","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neures.2021.05.011","volume":"173","author":"A Noguchi","year":"2021","unstructured":"Noguchi A, Ito K, Uosaki Y, Ideta-Otsuka M, Igarashi K, Nakashima H et al (2021) Decreased Lamin B1 levels affect gene positioning and expression in postmitotic neurons. Neurosci Res 173:22\u201333. https:\/\/doi.org\/10.1016\/j.neures.2021.05.011","journal-title":"Neurosci Res"},{"key":"3018_CR53","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.celrep.2018.12.085","volume":"26","author":"F Paonessa","year":"2019","unstructured":"Paonessa F, Evans LD, Solanki R, Larrieu D, Wray S, Hardy J et al (2019) Microtubules deform the nuclear membrane and disrupt nucleocytoplasmic transport in Tau-mediated frontotemporal dementia. Cell Rep 26:582-593.e585. https:\/\/doi.org\/10.1016\/j.celrep.2018.12.085","journal-title":"Cell Rep"},{"key":"3018_CR54","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1093\/brain\/awab436","volume":"145","author":"L Peris","year":"2022","unstructured":"Peris L, Parato J, Qu X, Soleilhac JM, Lante F, Kumar A et al (2022) Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer\u2019s disease. Brain 145:2486\u20132506. https:\/\/doi.org\/10.1093\/brain\/awab436","journal-title":"Brain"},{"key":"3018_CR55","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","volume":"388","author":"P Scheltens","year":"2016","unstructured":"Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S et al (2016) Alzheimer\u2019s disease. Lancet 388:505\u2013517. https:\/\/doi.org\/10.1016\/S0140-6736(15)01124-1","journal-title":"Lancet"},{"key":"3018_CR56","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nmeth.1314","volume":"6","author":"EK Schmidt","year":"2009","unstructured":"Schmidt EK, Clavarino G, Ceppi M, Pierre P (2009) SUnSET, a nonradioactive method to monitor protein synthesis. Nat Methods 6:275\u2013277. https:\/\/doi.org\/10.1038\/nmeth.1314","journal-title":"Nat Methods"},{"key":"3018_CR57","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.neuroscience.2022.04.017","volume":"518","author":"L Schulz","year":"2023","unstructured":"Schulz L, Ramirez P, Lemieux A, Gonzalez E, Thomson T, Frost B (2023) Tau-induced elevation of the activity-regulated cytoskeleton associated protein Arc1 causally mediates neurodegeneration in the adult Drosophila brain. Neuroscience 518:101\u2013111. https:\/\/doi.org\/10.1016\/j.neuroscience.2022.04.017","journal-title":"Neuroscience"},{"key":"3018_CR58","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00083","volume":"9","author":"SS Shafiei","year":"2017","unstructured":"Shafiei SS, Guerrero-Mu\u00f1oz MJ, Castillo-Carranza DL (2017) Tau oligomers: cytotoxicity, propagation, and mitochondrial damage. Front Aging Neurosci 9:83. https:\/\/doi.org\/10.3389\/fnagi.2017.00083","journal-title":"Front Aging Neurosci"},{"key":"3018_CR59","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1007\/s12035-024-04331-0","volume":"62","author":"H Sharma","year":"2025","unstructured":"Sharma H, Koirala S, Chew YL, Konopka A (2025) DNA damage and chromatin rearrangement work together to promote neurodegeneration. Mol Neurobiol 62:1282\u20131290. https:\/\/doi.org\/10.1007\/s12035-024-04331-0","journal-title":"Mol Neurobiol"},{"key":"3018_CR60","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41586-021-03911-7","volume":"598","author":"Y Shi","year":"2021","unstructured":"Shi Y, Zhang W, Yang Y, Murzin AG, Falcon B, Kotecha A et al (2021) Structure-based classification of tauopathies. Nature 598:359\u2013363. https:\/\/doi.org\/10.1038\/s41586-021-03911-7","journal-title":"Nature"},{"key":"3018_CR61","doi-asserted-by":"publisher","first-page":"3409","DOI":"10.1101\/gad.1735208","volume":"22","author":"T Shimi","year":"2008","unstructured":"Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE et al (2008) The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev 22:3409\u20133421. https:\/\/doi.org\/10.1101\/gad.1735208","journal-title":"Genes Dev"},{"key":"3018_CR62","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2023.1058968","volume":"4","author":"C Sohn","year":"2023","unstructured":"Sohn C, Ma J, Ray WJ, Frost B (2023) Pathogenic tau decreases nuclear tension in cultured neurons. Front Aging Neurosci 4:1058968. https:\/\/doi.org\/10.3389\/fragi.2023.1058968","journal-title":"Front Aging Neurosci"},{"key":"3018_CR63","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.cell.2013.01.009","volume":"152","author":"I Solovei","year":"2013","unstructured":"Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, Zwerger M et al (2013) LBR and lamin A\/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell 152:584\u2013598. https:\/\/doi.org\/10.1016\/j.cell.2013.01.009","journal-title":"Cell"},{"key":"3018_CR64","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1016\/j.neurobiolaging.2005.06.007","volume":"27","author":"MS Song","year":"2006","unstructured":"Song MS, Saavedra L, de Chaves EI (2006) Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to A\u03b2 in distal axons. Neurobiol Aging 27:1224\u20131238. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2005.06.007","journal-title":"Neurobiol Aging"},{"key":"3018_CR65","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.cell.2017.04.022","volume":"169","author":"B van Steensel","year":"2017","unstructured":"van Steensel B, Belmont AS (2017) Lamina-associated domains: links with chromosome architecture, heterochromatin, and gene repression. Cell 169:780\u2013791. https:\/\/doi.org\/10.1016\/j.cell.2017.04.022","journal-title":"Cell"},{"key":"3018_CR66","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nrn.2015.1","volume":"17","author":"Y Wang","year":"2016","unstructured":"Wang Y, Mandelkow E (2016) Tau in physiology and pathology. Nat Rev Neurosci 17:5\u201321. https:\/\/doi.org\/10.1038\/nrn.2015.1","journal-title":"Nat Rev Neurosci"},{"key":"3018_CR67","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1042\/BST20120134","volume":"40","author":"SM Ward","year":"2012","unstructured":"Ward SM, Himmelstein DS, Lancia JK, Binder LI (2012) Tau oligomers and tau toxicity in neurodegenerative disease. Biochem Soc Trans 40:667\u2013671. https:\/\/doi.org\/10.1042\/BST20120134","journal-title":"Biochem Soc Trans"},{"key":"3018_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-021-00270-1","volume":"10","author":"M Wu","year":"2021","unstructured":"Wu M, Zhang M, Yin X, Chen K, Hu Z, Zhou Q et al (2021) The role of pathological tau in synaptic dysfunction in Alzheimer\u2019s diseases. Transl Neurodegener 10:45. https:\/\/doi.org\/10.1186\/s40035-021-00270-1","journal-title":"Transl Neurodegener"},{"key":"3018_CR69","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","volume":"53","author":"Y Yoshiyama","year":"2007","unstructured":"Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC et al (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337\u2013351. https:\/\/doi.org\/10.1016\/j.neuron.2007.01.010","journal-title":"Neuron"},{"key":"3018_CR70","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01702-x","volume":"11","author":"N Younas","year":"2023","unstructured":"Younas N, Saleem T, Younas A, Zerr I (2023) Nuclear face of Tau: an inside player in neurodegeneration. Acta Neuropathol Commun 11:196. https:\/\/doi.org\/10.1186\/s40478-023-01702-x","journal-title":"Acta Neuropathol Commun"},{"key":"3018_CR71","doi-asserted-by":"publisher","first-page":"16103","DOI":"10.1074\/jbc.R112.354407","volume":"287","author":"SG Young","year":"2012","unstructured":"Young SG, Jung HJ, Coffinier C, Fong LG (2012) Understanding the roles of nuclear A- and B-type lamins in brain development. J Biol Chem 287:16103\u201316110. https:\/\/doi.org\/10.1074\/jbc.R112.354407","journal-title":"J Biol Chem"},{"key":"3018_CR72","doi-asserted-by":"publisher","first-page":"339","DOI":"10.4161\/nucl.2.5.17846","volume":"2","author":"N Zuleger","year":"2011","unstructured":"Zuleger N, Robson MI, Schirmer EC (2011) The nuclear envelope as a chromatin organizer. Nucleus 2:339\u2013349. https:\/\/doi.org\/10.4161\/nucl.2.5.17846","journal-title":"Nucleus"},{"key":"3018_CR73","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14245","volume":"23","author":"G Zuniga","year":"2024","unstructured":"Zuniga G, Katsumura S, De Mange J, Ramirez P, Atrian F, Morita M et al (2024) Pathogenic tau induces an adaptive elevation in mRNA translation rate at early stages of disease. Aging Cell 23:e14245. https:\/\/doi.org\/10.1111\/acel.14245","journal-title":"Aging Cell"}],"updated-by":[{"DOI":"10.1007\/s00401-026-03092-5","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000}}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03018-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-03018-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-026-03018-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:46:27Z","timestamp":1792557987000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-026-03018-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,22]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["3018"],"URL":"https:\/\/doi.org\/10.1007\/s00401-026-03018-1","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,22]]},"assertion":[{"value":"21 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised after the author name \u201cWeronika M. Gniadzik\u201d was mistakenly omitted from the author group. Now, it has been updated.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2026","order":9,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":10,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00401-026-03092-5","URL":"https:\/\/doi.org\/10.1007\/s00401-026-03092-5","order":12,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"43"}}