ArticleAnnals of neurology2023
Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer's Disease.
Article in Annals of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Etalanetug (E2814) in dominantly inherited Alzheimer's disease: an open-label phase 1b/2 study to assess safety and target engagement in participants with mild to moderate cognitive impairment.Alzheimer's research & therapy · 2026Trial
- 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
- Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial.BMJ neurology open · 2026Article
- Plasma levels of an N-terminal tau fragment predict Alzheimer's and neurodegenerative disease biomarkers in autosomal dominant Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- APOE isoform-associated tau oligomer polymorphs differ in synaptotoxicity and seeding activity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
- Synaptotoxic effects of extracellular tau are mediated by its microtubule-binding region.Acta neuropathologica · 2025Article
- Insights into pathophysiology, biomarkers, and therapeutics in tauopathies: Proceedings of the Tau2024 Global Conference.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.Frontiers in neurology · 2025Review
- Novel aspects of the phosphorylation and structure of pathological tau: implications for tauopathy biomarkers.FEBS open bio · 2024Review
Corrections and comments
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Authors and funding
31 authors at 13 institutions in 7 countries.
Funding
Abstract
objectiveIdentifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR-tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes. We examined the cerebrospinal fluid (CSF) MTBR-tau species in dominantly inherited Alzheimer's disease (DIAD) mutation carriers to assess the association with Alzheimer's disease (AD) biomarkers and clinical symptoms.
methodsCross-sectional and longitudinal CSF from 229 DIAD mutation carriers and 130 mutation non-carriers had sequential characterization of N-terminal/mid-domain phosphorylated tau (p-tau) followed by MTBR-tau species and tau positron emission tomography (tau PET), other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy.
resultsCSF MTBR-tau species located within the putative "border" region and one species corresponding to the "core" region of aggregates in neurofibrillary tangles (NFTs) increased during the presymptomatic stage and decreased during the symptomatic stage. The "border" MTBR-tau species were associated with amyloid pathology and CSF p-tau; whereas the "core" MTBR-tau species were associated stronger with tau PET and CSF measures of neurodegeneration. The ratio of the border to the core species provided a continuous measure of increasing amounts that tracked clinical progression and NFTs.
interpretationChanges in CSF soluble MTBR-tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R-specific MTBR-tau (border) to the NFT (core) MTBR-tau species corresponds to the pathology of NFTs in DIAD and change with disease progression. The dynamics between different MTBR-tau species in the CSF may serve as a marker of tau-related disease progression and target engagement of anti-tau therapeutics. ANN NEUROL 2023;93:1158-1172.
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