Evidence map›Paper›PMID 36544221›Full record

ArticleAlzheimer's research & therapy2022

CSF tau368/total-tau ratio reflects cognitive performance and neocortical tau better compared to p-tau181 and p-tau217 in cognitively impaired individuals.

Joel Simrén, Wagner S Brum, Nicholas J Ashton, Andrea L Benedet, Thomas K Karikari, Hlin Kvartsberg, Emma Sjons, Firoza Z Lussier, Mira Chamoun, Jenna Stevenson and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  4. The roles of biomarkers in Alzheimer's disease clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  5. Article
  6. Potential utility of plasma pTau217 for assessing amyloid and tau biomarker profiles.European journal of nuclear medicine and molecular imaging · 2025
    Article
  7. Article
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  9. Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 9 institutions in 5 countries.

Joel SimrénDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. joel.simren@gu.se.
Wagner S BrumDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Nicholas J AshtonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Andrea L BenedetDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Thomas K KarikariDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Hlin KvartsbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Emma SjonsDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Firoza Z LussierTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Mira ChamounTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Jenna StevensonTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Robert HopewellTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Vanessa PallenTranslational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Keqiang YeDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Tharick A PascoalDepartment of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, USA.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Pedro Rosa-Neto *Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Kaj Blennow *Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
University of Gothenburg · SEMontreal Neurological Institute and Hospital · CASahlgrenska University Hospital · SEUniversity of Pittsburgh · USCentre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-Montréal · CACentre Intégré Universitaire de Santé et de Services Sociaux du Saguenay–Lac-Saint-Jean · CAEmory University · USMcGill University · CAUniversidade Federal do Rio Grande do Sul · BR

Funding

Longitudinal multicenter head-to-head harmonization of tau PET tracersR01AG073267 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAKER, SUZANNE L, PASCOAL, THARICK · 2021 to 2025
$41.1M
Head-to-head comparisons of high-performance plasma phospho-tau epitopes for the detection of Alzheimer's diseaseR01AG075336 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Tharick Pascoal · 2022 to 2026
$3.7M
The effects of iron on oxidative stress and Alzheimer's biomarkers in amyloid-positive and negative elderly normalR01AG068398 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHIANG, GLORIA CHIA-YI · 2020 to 2024
$2.8M
CIHR MOP-11-51-31NIA NIH HHS R01 AG068398NIA NIH HHS R01 AG073267NIA NIH HHS R01 AG075336
6 · The paper itself

Abstract

introductionCerebrospinal fluid (CSF) tau biomarkers are reliable diagnostic markers for Alzheimer's disease (AD). However, their strong association with amyloid pathology may limit their reliability as specific markers of tau neurofibrillary tangles. A recent study showed evidence that a ratio of CSF C-terminally truncated tau (tau368, a tangle-enriched tau species), especially in ratio with total tau (t-tau), correlates strongly with tau PET tracer uptake. In this study, we set to evaluate the performance of the tau368/t-tau ratio in capturing tangle pathology, as indexed by a high-affinity tau PET tracer, as well as its association with severity of clinical symptoms.

methodsIn total, 125 participants were evaluated cross-sectionally from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort (21 young, 60 cognitively unimpaired [CU] elderly [15 Aβ+], 10 Aβ+ with mild cognitive impairment [MCI], 14 AD dementia patients, and 20 Aβ- individuals with non-AD cognitive disorders). All participants underwent amyloid and tau PET scanning, with [

resultsCSF tau368 concentration was not significantly different across the diagnostic groups, although a modest increase was observed in all groups as compared with healthy young individuals (all P < 0.01). In contrast, the CSF tau368/t-tau ratio was the lowest in AD dementia, being significantly lower than in CU individuals (Aβ-, P < 0.001; Aβ+, P < 0.01), as well as compared to those with non-AD cognitive disorders (P < 0.001). Notably, in individuals with symptomatic AD, tau368/t-tau correlated more strongly with [

conclusionThe tau368/t-tau ratio captures novel aspects of AD pathophysiology and disease severity in comparison to established CSF tau biomarkers, as it is more closely related to tau PET SUVR and cognitive performance in the symptomatic phase of the disease.

Indexed as

Alzheimer DiseaseCognitive DysfunctionNeocortextau ProteinsAgedAmyloid beta-PeptidesBiomarkersCognitionHumansPositron-Emission TomographyReproducibility of ResultsAmyloid beta-PeptidesBiomarkerstau Proteins

Identifiers

PMID36544221
PMCPMC9773470
OpenAlexW4312128886

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.