Creekmore, B. C., Watanabe, R. & Lee, E. B. Neurodegenerative Disease Tauopathies. Annu. Rev. Pathol. 19, 345–370 (2024).

Article  CAS  PubMed  Google Scholar 

Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H. & Del Tredici, K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 112, 389–404 (2006).

Article  PubMed  PubMed Central  Google Scholar 

Ghetti, B. et al. Invited review: frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging. Neuropathol. Appl. Neurobiol. 41, 24–46 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kovacs, G. G. et al. Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol. https://doi.org/10.1007/s00401-020-02158-2 (2020).

Zhang, W. et al. Novel tau filament fold in corticobasal degeneration. Nature 580, 283–287 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin, Y. et al. Amyloid-β-targeting immunotherapies for Alzheimer’s disease. J. Control. Release 375, 346–365 (2024).

Article  CAS  PubMed  Google Scholar 

Wilson, D. M. et al. Hallmarks of neurodegenerative diseases. Cell 186, 693–714 (2023).

Article  CAS  PubMed  Google Scholar 

Hu, J. et al. Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer’s disease. Neuron https://doi.org/10.1016/j.neuron.2022.10.021 (2023).

Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337–351 (2007).

Article  CAS  PubMed  Google Scholar 

Merchán-Rubira, J., Sebastián-Serrano, Á, Díaz-Hernández, M., Avila, J. & Hernández, F. Peripheral nervous system effects in the PS19 tau transgenic mouse model of tauopathy. Neurosci. Lett. 698, 204–208 (2019).

Article  PubMed  Google Scholar 

Zhang, T. et al. Influenza virus Z-RNAs induce ZBP1-mediated necroptosis. Cell https://doi.org/10.1016/j.cell.2020.02.050 (2020).

Caccamo, A. et al. Necroptosis activation in Alzheimer’s disease. Nat. Neurosci. 20, 1236–1246 (2017).

Article  CAS  PubMed  Google Scholar 

Balusu, S. et al. MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease. Science 381, 1176–1182 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mila-Aloma, M. et al. Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease. Nat. Med. 28, 1797–1801 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Prissette, M. et al. Disruption of nuclear envelope integrity as a possible initiating event in tauopathies. Cell Rep. 40, 111249 (2022).

Article  CAS  PubMed  Google Scholar 

Manczak, M. & Reddy, P. H. Abnormal interaction of oligomeric amyloid-β with phosphorylated tau: implications to synaptic dysfunction and neuronal damage. J. Alzheimers Dis. 36, 285–295 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rauch, J. N. et al. LRP1 is a master regulator of tau uptake and spread. Nature 580, 381–385 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mellone, M. et al. Tau pathology is present in vivo and develops in vitro in sensory neurons from human P301S tau transgenic mice: a system for screening drugs against tauopathies. J. Neurosci. 33, 18175–18189 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, R. et al. Gut stem cell necroptosis by genome instability triggers bowel inflammation. Nature 580, 386–390 (2020).

Article  CAS  PubMed  Google Scholar 

Yang, Z.-H. et al. ZBP1 senses splicing aberration through Z-RNA to promote cell death. Mol. Cell https://doi.org/10.1016/j.molcel.2025.03.023 (2025).

Cai, Z.-Y. et al. A ZBP1 isoform blocks ZBP1-mediated cell death. Cell Rep. 43, 114221 (2024).

Article  CAS  PubMed  Google Scholar 

Maelfait, J. et al. Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis. EMBO J. 36, 2529–2543 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sanders, D. W. et al. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82, 1271–1288 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Riegerová, P. et al. Expression and Localization of AβPP in SH-SY5Y cells depends on differentiation state. J. Alzheimers Dis. 82, 485–491 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Khlistunova, I. et al. Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J. Biol. Chem. 281, 1205–1214 (2006).

Article  CAS  PubMed  Google Scholar 

Wischik, C. M. et al. Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc. Natl Acad. Sci. USA 85, 4506–4510 (1988).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Styren, S. D., Hamilton, R. L., Styren, G. C. & Klunk, W. E. X-34, a fluorescent derivative of Congo red: a novel histochemical stain for Alzheimer’s disease pathology. J. Histochem. Cytochem. 48, 1223–1232 (2000).

Article  CAS  PubMed  Google Scholar 

DeVos, S. L. et al. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aag0481 (2017).

Krall, J. B., Nichols, P. J., Henen, M. A., Vicens, Q. & Vögeli, B. Structure and formation of Z-DNA and Z-RNA. Molecules https://doi.org/10.3390/molecules28020843 (2023).

Wang, A. J. et al. Left-handed double helical DNA: variations in the backbone conformation. Science 211, 171–176 (1981).

Article  CAS  PubMed  Google Scholar 

Zhang, H. et al. Nuclear lamina erosion-induced resurrection of endogenous retroviruses underlies neuronal aging. Cell Rep. 42, 112593 (2023).

Article  CAS  PubMed  Google Scholar 

Reilly, M. T., Faulkner, G. J., Dubnau, J., Ponomarev, I. & Gage, F. H. The role of transposable elements in health and diseases of the central nervous system. J. Neurosci. 33, 17577–17586 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Towbin, B. D. et al. Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell 150, 934–947 (2012).

Article  CAS  PubMed  Google Scholar 

Padeken, J., Methot, S. P. & Gasser, S. M. Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance. Nat. Rev. Mol. Cell Biol. 23, 623–640 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Siegenfeld, A. P. et al. Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery. Nat. Commun. 13, 4199 (2022).

Article  CAS