N-terminally acetylated Met11-Tau: a new pathological truncated Tau species with functional relevance in Alzheimer Disease
Guedjdal, S.; Leghay, C.; Derisbourg, M.; Eddarkaoui, S.; Lecerf, S.; Vermon, F.; Caillierez, R.; Begard, S.; Regost, C.; Laloux, C.; da Costa, P. J.; Carvalho, K.; Chiappetta, G.; Verdier, Y.; Buee-Scherrer, V.; Deramecourt, V.; Schraen, S.; Blum, D.; MARTIN, F.; Buee, L.; Hamdane, M.
Show abstract
Neurodegenerative diseases like Alzheimers disease (AD) are characterized by progressive accumulation of pathological Tau proteins. Among the diverse Tau species, truncated variants are emerging as key contributors, yet their identity remains elusive, particularly for the N-terminal truncated ones. The present study identifies and characterizes a novel N-terminally truncated and N-alpha-acetylated form of the Tau protein. Using a newly developed antibody specifically targeting this truncated variant, we demonstrate that this species accumulates early in degenerating neurons in both transgenic mouse models of AD-related Tau pathology and post-mortem brain tissues from AD patients. Importantly, in vivo functional experiments reveal that expression of this truncated Tau species exacerbates Tau pathology, whereas targeted immunotherapeutic with the specific antibody significantly reduces pathological Tau accumulation and prevents associated memory impairments. These findings position this newly identified Tau variant as both a marker of neurofibrillary degeneration and a pathogenic driver of neurodegeneration and supports its potential as a therapeutic target in Tau-related disorders, notably AD.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Tau seeding and spreading in vivo is supported by both AD-derived fibrillar and oligomeric tau 98%
- Loss of TMEM106B exacerbates Tau pathology and neurodegeneration in PS19 mice 96%
- Tau phosphorylated at serine 356 is associated with Alzheimer's disease pathology and can be lowered in mouse and human brain tissue using the NUAK inhibitor WZ4003 96%
Similar papers in this journal
- SETD7-mediated lysine monomethylation is abundant on non-hyperphosphorylated nuclear Tau 97%
- Probe-dependent Proximity Profiling (ProPPr) Uncovers Similarities and Differences in Phospho-Tau-Associated Proteomes Between Tauopathies 96%
- Amyloid plaque deposition accelerates tau propagation via activation of microglia in a humanized APP mouse model 96%
Similar papers in this journal
- Aβ oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer's disease. 97%
- C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimers disease 96%
- Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction, progression, and prion-like spread of Alzheimer s disease pathogenesis 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.