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Using immunohistochemistry, we demonstrated activated necroptosis-related proteins in transgenic mice developing Tau pathology and in primary neurons from amyloid precursor protein (APP)\u2013Tau double transgenic mice treated with phosphorylated Tau seeds derived from a patient with AD but not in APP transgenic mice that only exhibited \u03b2-amyloid deposits. Necroptosis proteins in granulovacuolar degeneration (GVD) bodies were associated with neuronal loss in mouse brain regions also known to be vulnerable to GVD in the human AD brain. Necroptosis inhibitors lowered the percentage of neurons showing GVD and reduced neuronal loss, both in transgenic mice and in primary mouse neurons. This suggests that a GVD-associated form of necroptosis that we refer to as \u201cGVD-necroptosis\u201d may represent a delayed form of necroptosis in AD. We propose that inhibition of necroptosis could rescue this type of neuronal death in AD.<\/jats:p>","DOI":"10.1126\/scitranslmed.adf5128","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:59:03Z","timestamp":1730296743000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":32,"title":["Inhibition of an Alzheimer\u2019s disease\u2013associated form of necroptosis rescues neuronal death in mouse models"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2255-6088","authenticated-orcid":true,"given":"Marta J.","family":"Koper","sequence":"first","affiliation":[{"name":"Laboratory for Neuropathology, Department of Imaging and Pathology, KU Leuven, Leuven Brain Institute (LBI), Leuven, Belgium."},{"name":"Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, KU Leuven, Leuven Brain Institute (LBI), Leuven, 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