biostudies-literatureTheofilas PNIA NIH HHSNINDS NIH HHSAlzheimer&amp;apos;s AssociationNational Institute on Aging103954https://www.ebi.ac.uk/biostudies/studies/S-EPMC11866097biostudies-literatureUnknown130<h4>Background</h4>Tau post-translational modifications (PTMs) result in the gradual build-up of abnormal tau and neuronal degeneration in tauopathies, encompassing variants of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Tau proteolytically cleaved by active caspases, including caspase-6, may be neurotoxic and prone to self-aggregation. Also, our recent findings show that caspase-6 truncated tau represents a frequent and understudied aspect of tau pathology in AD in addition to phospho-tau pathology. In AD and Pick's disease, a large percentage of caspase-6 associated cleaved-tau positive neurons lack phospho-tau, suggesting that many vulnerable neurons to tau pathology go undetected when using conventional phospho-tau antibodies and possibly will not respond to Molecular and cellular neurosciencesiPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death.PMC11866097K24 AG053435R01 AG054025R56 AG057528RF1 AG068125P30 AG062422P50 AG023501P01 AG019724U54 NS100717R01 AG075802K01 AG053433U54 NS123746Miller BLKayed RArkin MRTheofilas PWang CButler DGrinberg LTPetersen CNg RChin BTemple SKarch CMGestwicki JEGan LMorales DOAmbrose AYang TKhan SfalseiPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death.<h4>Background</h4>Tau post-translational modifications (PTMs) result in the gradual build-up of abnormal tau and neuronal degeneration in tauopathies, encompassing variants of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Tau proteolytically cleaved by active caspases, including caspase-6, may be neurotoxic and prone to self-aggregation. Also, our recent findings show that caspase-6 truncated tau represents a frequent and understudied aspect of tau pathology in AD in addition to phospho-tau pathology. In AD and Pick's disease, a large percentage of caspase-6 associated cleaved-tau positive neurons lack phospho-tau, suggesting that many vulnerable neurons to tau pathology go undetected when using conventional phospho-tau antibodies and possibly will not respond to 2024-01-01T00:00:00Z2024 Sep2026-05-28T22:23:25.225Z2026-04-08T03:19:22.941ZS-EPMC118660973903271910.1016/j.mcn.2024.103954