ArticleJournal of Alzheimer's disease : JAD2022
Site-Specific Cerebrospinal Fluid Tau Hyperphosphorylation in Response to Alzheimer's Disease Brain Pathology: Not All Tau Phospho-Sites are Hyperphosphorylated.
Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease.Acta neuropathologica · 2025Trial
- CSF p-tau205: a biomarker of Alzheimer's disease progression and biological staging.Molecular psychiatry · 2026Article
- CSF and plasma tau biomarkers in the Down syndrome-Alzheimer's disease continuum.EBioMedicine · 2026Article
- Evaluation of CSF and plasma tau species as fluid surrogate candidates for tau PET in prodromal to moderate Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Trajectories of plasma and CSF MTBR-tau243 and phosphorylated-tau species across the Alzheimer's disease continuum.Nature communications · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Tau protein in Parkinson's disease: advances in phosphoproteomics and molecular dynamics simulations.Frontiers in aging neuroscience · 2026Review
- P-TAU205 IS A BIOMARKER LINKED TO TAU-PET ABNORMALITY: A CROSS-SECTIONAL AND LONGITUDINAL STUDY.medRxiv : the preprint server for health sciences · 2025Article
- Ruling in, ruling out: the clinical utility of plasma biomarkers in diagnosis of Alzheimer's disease.The Journal of clinical investigation · 2025Article
- A novel pThr217 tau monoclonal antibody reveals neuropathological heterogeneity in tauopathies.Scientific reports · 2025Article
- Predicting continuous amyloid PET values with CSF tau phosphorylation occupancies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- P-tau217 as a Reliable Blood-Based Marker of Alzheimer's Disease.Biomedicines · 2024Review
- Is blood pTau a reliable indicator of the CSF status? A narrative review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Biochemical approaches to assess the impact of post-translational modifications on pathogenic tau conformations using recombinant protein.Biochemical Society transactions · 2024Review
- Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer's Disease.Molecular neurodegeneration · 2024Article
- Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer's disease pathology.Molecular neurodegeneration · 2024Article
- CSF p-tau205: a biomarker of tau pathology in Alzheimer's disease.Acta neuropathologica · 2024Article
- Evaluation of partial volume correction and analysis of longitudinal [Frontiers in neuroimaging · 2024Article
- Comparison of cerebrospinal fluid, plasma and neuroimaging biomarker utility in Alzheimer's disease.Brain communications · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUnderstanding patterns of association between CSF phosphorylated tau (p-tau) species and clinical disease severity will aid Alzheimer's disease (AD) diagnosis and treatment.
objectiveTo evaluate changes in tau phosphorylation ratios to brain imaging (amyloid PET, [18F]GTP1 PET, and MRI) and cognition across clinical stages of AD in two different cohorts.
methodsA mass spectrometry (MS)-based method was used to evaluate the relationship between p-tau/tau phosphorylation ratios on 11 sites in CSF and AD pathology measured by tau PET ([18F]GTP1) and amyloid PET ([18F]florbetapir or [18F]florbetaben). Cohort A included cognitively normal amyloid negative (n = 6) and positive (n = 5) individuals, and amyloid positive prodromal (n = 13), mild (n = 12), and moderate AD patients (n = 10); and Cohort B included amyloid positive prodromal (n = 24) and mild (n = 40) AD patients.
resultsIn this cross-sectional analysis, we identified clusters of phosphosites with different profiles of phosphorylation ratios across stages of disease. Eight of 11 investigated sites were hyperphosphorylated and associated with SUVR measures from [18F]GTP1 and amyloid PET. Novel sites 111, 153, and 208 may be relevant biomarkers for AD diagnosis to complement tau hyperphosphorylation measures on previously established sites 181, 205, 217, and 231. Hypophosphorylation was detected on residues 175, 199, and 202, and was inversely associated with [18F]GTP1 and amyloid PET.
conclusionHyperphosphorylated and hypophosphorylated forms of tau are associated with AD pathologies, and due to their different site-specific profiles, they may be used in combination to assist with staging of disease.
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