ArticleInternational journal of experimental pathology2008
Cleavage and conformational changes of tau protein follow phosphorylation during Alzheimer's disease.
Article in International journal of experimental pathology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 140 citations in OpenAlex.
- ApoE4 as a Therapeutic Target in Epilepsy: From Pathogenic Mechanisms to Precision Medicine.CNS neuroscience & therapeutics · 2026Review
- Tau pSer396 and pSer404 Define Distinct Epitope Regions Linked to Different Antibody Functions.bioRxiv : the preprint server for biology · 2026Article
- Pathological calcium influx through amyloid beta pores disrupts synaptic function.Cell calcium · 2025Article
- Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the APOE-Tau Axis via Human Cerebral Organoids with Immuno-SERS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Structures of ΔD421 Truncated Tau Fibrils.Journal of molecular biology · 2025Article
- Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders.Frontiers in aging neuroscience · 2025Review
- Vulnerability of the entorhinal cortex II to neurodegeneration in Alzheimer's disease.Brain communications · 2025Article
- Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease.Archiv der Pharmazie · 2025Review
- Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.Aging and disease · 2024Article
- Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- Distinct Molecular Signatures of Amyloid-Beta and Tau in Alzheimer's Disease Associated with Down Syndrome.International journal of molecular sciences · 2023Article
- Unravelling the mechanotransduction pathways in Alzheimer's disease.Journal of biological engineering · 2023Review
- JNK Activation in Alzheimer's Disease Is Driven by Amyloid β and Is Associated with Tau Pathology.ACS chemical neuroscience · 2023Article
- SIRT1 deficiency increases O-GlcNAcylation of tau, mediating synaptic tauopathy.Molecular psychiatry · 2022Article
- Upregulated CaCells · 2022Article
- SUMO1 Modification of Tau in Progressive Supranuclear Palsy.Molecular neurobiology · 2022Article
- Intrathecal amyloid-beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer's disease.Neuropathology and applied neurobiology · 2022Article
- Regulation of Neurodegeneration-associated Protein Fragments by the N-degron Pathways.Neurotoxicity research · 2022Review
- Key brain cell interactions and contributions to the pathogenesis of Alzheimer's disease.Frontiers in cell and developmental biology · 2022Review
- Alzheimer's disease is an inherent, natural part of human brain aging: an integrated perspective.Free neuropathology · 2022Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Phosphorylation, cleavage and conformational changes in tau protein all play pivotal roles during Alzheimer's disease (AD). In an effort to determine the chronological sequence of these changes, in this study, using confocal microscopy, we compared phosphorylation at several sites (Ser(199/202/396/404/422)-Thr(205) and the second repeat domain), cleavage of tau (D(421)) and the canonical conformational Alz-50 epitope. While all of these posttranslational modifications are found in neurofibrillary tangles (NFTs) at all stages of the disease, we found significantly higher numbers of phospho-tau positive NFTs when compared with cleaved tau (P = 0.006 in Braak III; P = 0.002 in Braak IV; P = 0.012 in Braak V) or compared with the Alz-50 epitope (P < 0.05). Consistent with these findings, in a double transgenic mice model (Tet/GSK-3beta/VLW) overexpressing the enzyme glycogen synthase kinase-3beta (GSK-3beta) and tau with a triple FTDP-17 mutation (VLW) with AD-like neurodegeneration, phosphorylation at sites Ser(199/202)-Thr(205) was greater than truncated tau. Taken together, these data strongly support the notion that the conformational changes and truncation of tau occur after the phosphorylation of tau. We propose two probable pathways for the pathological processing of tau protein during AD, either phosphorylation and cleavage of tau followed by the Alz-50 conformational change or phosphorylation followed by the conformational change and cleavage as the last step.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.