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Adv."],"published-print":{"date-parts":[[2026,3,6]]},"abstract":"<jats:p>\n                    In Alzheimer\u2019s disease, many surviving neurons with tau pathology contain granulovacuolar degeneration bodies (GVBs), neuron-specific lysosomal structures induced by pathological tau assemblies. This could indicate a neuroprotective role for GVBs; however, the mechanism of GVB formation and its functional implications are elusive. Here, we demonstrate that casein kinase 1\u03b4 (CK1\u03b4) activity is required for GVB formation. CK1\u03b4 is sequestered in the GVB during this process in an autophagy-dependent manner. We show that neurons with GVBs (GVB\n                    <jats:sup>+<\/jats:sup>\n                    ) are resilient to tau-induced impairment of global protein synthesis and are protected against tau-mediated neurodegeneration. GVB\n                    <jats:sup>+<\/jats:sup>\n                    neurons do not exhibit differential activation of transient translational stress responses but have increased ribosomal content. Unlike neurons without GVBs, GVB\n                    <jats:sup>+<\/jats:sup>\n                    neurons fully retain the capacity to induce long-term potentiation\u2013induced protein synthesis in the presence of tau pathology. Our results have identified CK1\u03b4 as a key regulator of GVB formation that confers a protective neuron-specific stress response to tau pathology. These findings provide opportunities for targeting neuronal resilience in tauopathies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea8940","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T18:58:34Z","timestamp":1772823514000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Neurons with granulovacuolar degeneration bodies are resilient to tau-induced protein synthesis impairment"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5744-7291","authenticated-orcid":true,"given":"Jasper F. M.","family":"Smits","sequence":"first","affiliation":[{"name":"Dept. of Human Genetics, Amsterdam UMC - Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."},{"name":"Dept. of Functional Genomics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7573-0177","authenticated-orcid":true,"given":"Thijmen W.","family":"Ligthart","sequence":"additional","affiliation":[{"name":"Dept. of Human Genetics, Amsterdam UMC - Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."},{"name":"Dept. of Functional Genomics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9684-1047","authenticated-orcid":true,"given":"Marta","family":"Jorge-Oliva","sequence":"additional","affiliation":[{"name":"Dept. of Functional Genomics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skip","family":"Middelhoff","sequence":"additional","affiliation":[{"name":"Dept. of Human Genetics, Amsterdam UMC - Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."},{"name":"Dept. of Functional Genomics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7496-8841","authenticated-orcid":true,"given":"Fleur","family":"Schipper","sequence":"additional","affiliation":[{"name":"Dept. of Functional Genomics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7954-8967","authenticated-orcid":true,"given":"D\u00e9bora","family":"Pita-Illobre","sequence":"additional","affiliation":[{"name":"Dept. of Molecular and Cellular Neuroscience, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6983-5055","authenticated-orcid":true,"given":"Ka Wan","family":"Li","sequence":"additional","affiliation":[{"name":"Dept. of Molecular and Cellular Neuroscience, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1431-4559","authenticated-orcid":true,"given":"Wiep","family":"Scheper","sequence":"additional","affiliation":[{"name":"Dept. of Human Genetics, Amsterdam UMC - 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