ArticleActa neuropathologica communications2019
A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer's disease brain.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 119 citations in OpenAlex.
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- Misfolded Proteins and Cognitive Decline: Mechanistic Insights into Neurodegenerative Disorders.Neurology international · 2026Review
- Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC-Derived Cortical Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Probing tau citrullination in Alzheimer's disease brains and mouse models of tauopathy.Acta neuropathologica · 2025Article
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- Locus coeruleus-entorhinal cortex tract integrity is linked to plasma tau and glial fibrillary acidic protein.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Unlocking the Sugar Code: Implications and Consequences of Glycosylation in Alzheimer's Disease and Other Tauopathies.Biomedicines · 2025Review
- Tau-Mitochondria Interactions in Neurodegeneration: Mechanisms and Therapeutic Potential.Cellular and molecular neurobiology · 2025Review
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Neocortical tau propagation is a mediator of clinical heterogeneity in Alzheimer's disease.Molecular psychiatry · 2025Article
- Review
- Seeding-competent early tau multimers are associated with cell type-specific transcriptional signatures.Acta neuropathologica · 2025Article
- Vulnerability of the entorhinal cortex II to neurodegeneration in Alzheimer's disease.Brain communications · 2025Article
- Innovations in Alzheimer's disease diagnostic technologies: clinical prospects of novel biomarkers, multimodal integration, and non-invasive detection.Frontiers in neurology · 2025Review
- Precision Medicine in Neurodegenerative Diseases: Genomic Approaches to Target Amyloid-β, Tau, and Alpha-Synuclein Pathways.Current genomics · 2025Review
- Plasma p-tau immunoassays in clinical research for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- TYK2 regulates tau levels, phosphorylation and aggregation in a tauopathy mouse model.Nature neuroscience · 2024Article
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- A multi-targeting immunotherapy ameliorates multiple facets of Alzheimer's disease in 3xTg mice.NPJ vaccines · 2024Article
- Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Tau is a microtubule-binding protein that can receive various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Hyperphosphorylation of tau is linked to its aggregation and the formation of neurofibrillary tangles (NFTs), which are a hallmark of Alzheimer's disease (AD). While more than 70 phosphorylation sites have been detected previously on NFT tau, studies of oligomeric and detergent-soluble tau in human brains during the early stages of AD are lacking. Here we apply a comprehensive electrochemiluminescence ELISA assay to analyze twenty-five different PTM sites as well as tau oligomerization in control and sporadic AD brain. The samples were classified as Braak stages 0-I, II or III-IV, corresponding to the progression of microscopically detectable tau pathology throughout different brain regions. We found that soluble tau multimers are strongly increased at Braak stages III-IV in all brain regions under investigation, including the temporal cortex, which does not contain NFTs or misfolded oligomers at this stage of pathology. We additionally identified five phosphorylation sites that are specifically and consistently increased across the entorhinal cortex, hippocampus and temporal cortex in the same donors. Three of these sites correlate with tau multimerization in all three brain regions, but do not overlap with the epitopes of phospho-sensitive antibodies commonly used for the immunohistochemical detection of NFTs. Our results thus suggest that soluble multimers are characterized by a small set of specific phosphorylation events that differ from those dominating in mature NFTs. These findings shed light on early PTM changes of tau during AD pathogenesis in human brains.
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