ArticleAnnals of clinical and translational neurology2021
MAPT R406W increases tau T217 phosphorylation in absence of amyloid pathology.
Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Integrating multi-modal biological knowledge via contrastive dual-view graph learning for phosphorylation site-disease association prediction.Bioinformatics (Oxford, England) · 2026Article
- Tau pathology in epilepsy: emerging mechanisms and translational opportunities.Brain : a journal of neurology · 2026Review
- Developmental brain programmes and biomarker activation in Alzheimer's disease.Brain communications · 2026Review
- A novel pThr217 tau monoclonal antibody reveals neuropathological heterogeneity in tauopathies.Scientific reports · 2025Article
- Differentiating Progressive Supranuclear Palsy and Corticobasal Syndrome: Insights from Cerebrospinal Fluid Biomarkers-A Narrative Review.Medicina (Kaunas, Lithuania) · 2025Review
- Plasma p-tau immunoassays in clinical research for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Fluid biomarkers in familial frontotemporal dementia: progress and prospects.Frontiers in neurology · 2025Review
- Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers.FEBS open bio · 2024Review
- Plasma phosphorylated-tau217 is increased in Niemann-Pick disease type C.Brain communications · 2024Article
- Frontotemporal lobar degeneration.Nature reviews. Disease primers · 2023Review
- Patients carrying the mutation p.R406W in MAPT present with non-conforming phenotypic spectrum.Brain : a journal of neurology · 2023Article
- Neural atrophy produced by AAV tau injections into hippocampus and anterior cortex of middle-aged mice.Neurobiology of aging · 2023Article
- CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer's disease.Nature aging · 2023Article
- Plasma phospho-tau in Alzheimer's disease: towards diagnostic and therapeutic trial applications.Molecular neurodegeneration · 2023Review
- Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility.Nature reviews. Neurology · 2022Review
- Dissecting the clinical heterogeneity of early-onset Alzheimer's disease.Molecular psychiatry · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveTau hyperphosphorylation at threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer's disease (AD). However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, CSF pT217 was measured in AD and other tauopathies.
methodsUsing immunoprecipitation and mass spectrometry methods, we compared CSF T217 phosphorylation occupancy (pT217/T217) and amyloid-beta (Aβ) 42/40 ratio in cognitively normal individuals and those with symptomatic AD, progressive supranuclear palsy, corticobasal syndrome, and sporadic and familial frontotemporal dementia.
resultsIndividuals with AD had high CSF pT217/T217 and low Aβ42/40. In contrast, cognitively normal individuals and the majority of those with 4R tauopathies had low CSF pT217/T217 and normal Aβ 42/40. We identified a subgroup of individuals with increased CSF pT217/T217 and normal Aβ 42/40 ratio, most of whom were MAPT R406W mutation carriers. Diagnostic accuracies of CSF Aβ 42/40 and CSF pT217/T217, alone and in combination were compared. We show that CSF pT217/T217 × CSF Aβ 42/40 is a sensitive composite biomarker that can separate MAPT R406W carriers from cognitively normal individuals and those with other tauopathies.
interpretationMAPT R406W is a tau mutation that leads to 3R+4R tauopathy similar to AD, but without amyloid neuropathology. These findings suggest that change in CSF pT217/T217 ratio is not specific to AD and might reflect common downstream tau pathophysiology common to 3R+4R tauopathies.
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Registered trials
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