ArticlePloS one2013
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Trial
- Using Drosophila to identify naturally occurring genetic modifiers of amyloid beta 42- and tau-induced toxicity.G3 (Bethesda, Md.) · 2023Article
- Article
- Human Tau Isoforms and Proteolysis for Production of Toxic Tau Fragments in Neurodegeneration.Frontiers in neuroscience · 2021Review
- Truncation of Tau selectively facilitates its pathological activities.The Journal of biological chemistry · 2020Article
- Matrix metalloproteinase-degraded type I collagen is associated withNeurology. Genetics · 2020Article
- A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals.Scientific reports · 2020Article
- Cellular Biology of Tau Diversity and Pathogenic Conformers.Frontiers in neurology · 2020Review
- Article
- Observational
- Tau Proteolysis in the Pathogenesis of Tauopathies: Neurotoxic Fragments and Novel Biomarkers.Journal of Alzheimer's disease : JAD · 2018Review
- Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: A prospective study.PloS one · 2018Observational
- Tau Diagnostics and Clinical Studies.Journal of molecular neuroscience : MN · 2017Article
- Co-expression of truncated and full-length tau induces severe neurotoxicity.Molecular psychiatry · 2016Article
- Expert consensus document: Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions.Nature reviews. Neurology · 2015Review
- Blood-Based Proteomic Biomarkers of Alzheimer's Disease Pathology.Frontiers in neurology · 2015Review
- The potential of pathological protein fragmentation in blood-based biomarker development for dementia - with emphasis on Alzheimer's disease.Frontiers in neurology · 2015Review
- Developing novel blood-based biomarkers for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2014Review
- The future of blood-based biomarkers for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2014Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAlzheimer's disease (AD) is a devastating neurological disease characterized by pathological proteolytic cleavage of tau protein, which appears to initiate death of the neurons. The objective of this study was to investigate whether a proteolytic fragment of the tau protein could serve as blood-based biomarker of cognitive function in AD.
methodsWe developed a highly sensitive ELISA assay specifically detecting an A Disintegrin and Metalloproteinase 10 (ADAM10)-generated fragment of tau (Tau-A). We characterized the assay in detail with to respect specificity and reactivity in healthy human serum. We used samples from the Tg4510 tau transgenic mice, which over-express the tau mutant P301L and exhibit a tauopathy with similarities to that observed in AD. We used serum samples from 21 well-characterized Alzheimer's patients, and we correlated the Tau-A levels to cognitive function.
resultsThe Tau-A ELISA specifically detected the cleavage sequence at the N-terminus of a fragment of tau generated by ADAM10 with no cross-reactivity to intact tau or brain extracts. In brain extracts from Tg4510 mice compared to wt controls we found 10-fold higher levels of Tau-A (p<0.001), which indicates a pathological relevance of this marker. In serum from healthy individuals we found robust and reproducible levels of Tau-A, indicating that the analyte is present in serum. In serum from AD patients an inverse correlation (R² = 0.46, p<0.001) between the cognitive assessment score (Mattis Dementia Rating Scale (MDRS)) and Tau-A levels was observed.
conclusionBased on the hypothesis that tau is cleaved proteolytically and then released into the blood, we here provide evidence for the presence of an ADAM10-generated tau fragment (Tau-A) in serum. In addition, the levels of Tau-A showed an inverse correlation to cognitive function, which could indicate that this marker is a serum marker with pathological relevance for AD.
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