Evidence map›Paper›PMID 27296779›Full record

ArticleActa neuropathologica communications2016

An autoradiographic evaluation of AV-1451 Tau PET in dementia.

Val J Lowe, Geoffry Curran, Ping Fang, Amanda M Liesinger, Keith A Josephs, Joseph E Parisi, Kejal Kantarci, Bradley F Boeve, Mukesh K Pandey, Tyler Bruinsma and 9 more

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in Acta neuropathologica communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 318 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
318citing papers in PubMed, 5 pooled it
37.8field-weighted citation impact, top 1% 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

318 citing papers in PubMed, 5 syntheses or guidelines pooled it, 478 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Evaluation of [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
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  15. Correlation between in vivoAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  16. Review
  17. Subtracting First Principal Component May Improve 4R Tau Detectability on [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026
    Article
  18. Evaluation of [Acta neuropathologica communications · 2026
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  19. Association of [Neurology · 2026
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  20. Neuronal alkaline phosphatase promotes the spread of Tau-induced pathology, and its blockade prevents neurodegeneration and memory loss.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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258 more citing papers are in PubMed but not listed here.

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

19 authors at 4 institutions in 1 country.

Val J LoweDepartment of Radiology, Mayo Clinic, Rochester, MN, USA. vlowe@mayo.edu.
Geoffry CurranDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Ping FangDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Amanda M LiesingerDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Keith A JosephsDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Joseph E ParisiDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Kejal KantarciDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Mukesh K PandeyDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Tyler BruinsmaDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
David S KnopmanDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
David T JonesDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Leonard PetrucelliDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Casey N CookDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Mayo Clinic in Arizona · USMayo Clinic in Florida · USJacksonville College · USMayo Clinic · US

Funding

SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9M
Neuropathology CoreP50NS072187 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2010 to 2017
$8.7M
Validating the New Criteria for Preclinical Alzheimer's diseaseR01AG041851 · NIA · MAYO CLINIC ROCHESTER · PI JACK, CLIFFORD R., KNOPMAN, DAVID S · 2012 to 2021
$6.3M
Sex-specific Risk for Vascular Dysfunction and Cognitive DeclineP50AG044170 · NIA · MAYO CLINIC ROCHESTER · PI MILLER, VIRGINIA M · 2012 to 2017
$6.1M
Longitudinal Multi-modal Imaging in Progressive Supranuclear Palsy SyndromesR01NS089757 · NINDS · MAYO CLINIC ROCHESTER · PI JOSEPHS, KEITH A, WHITWELL, JENNIFER LOUISE · 2015 to 2024
$5.6M
The role of acetylation in regulating pathophysiology of tauR01NS089544 · NINDS · MAYO CLINIC JACKSONVILLE · PI PETRUCELLI, LEONARD, WOLOZIN, BENJAMIN L · 2014 to 2018
$1.9M
PIB PET Scanning in Speech and Language Based DementiasR01DC010367 · NIDCD · MAYO CLINIC ROCHESTER · PI JOSEPHS, KEITH A · 2010 to 2014
$1.7M
Manipulating tau's posttranslational modifications to block disease progression in vivoR21NS094489 · NINDS · MAYO CLINIC JACKSONVILLE · PI COOK, CASEY N · 2015 to 2016
$430k
NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG044170NIA NIH HHS R01 AG041851NIA NIH HHS U01 AG006786NIDCD NIH HHS R01 DC010367NINDS NIH HHS P50 NS072187NINDS NIH HHS R01 NS089544NINDS NIH HHS R01 NS089757NINDS NIH HHS R21 NS094489
6 · The paper itself

Abstract

backgroundIt is essential to determine the specificity of AV-1451 PET for tau in brain imaging by using pathological comparisons. We performed autoradiography in autopsy-confirmed Alzheimer disease and other neurodegenerative disorders to evaluate the specificity of AV-1451 binding for tau aggregates.

methodsTissue samples were selected that had a variety of dementia-related neuropathologies including Alzheimer disease, primary age-related tauopathy, tangle predominant dementia, non-Alzheimer disease tauopathies, frontotemporal dementia, parkinsonism, Lewy body disease and multiple system atrophy (n = 38). Brain tissue sections were stained for tau, TAR DNA-binding protein-43, and α-synuclein and compared to AV-1451 autoradiography on adjacent sections.

resultsAV-1451 preferentially localized to neurofibrillary tangles, with less binding to areas enriched in neuritic pathology and less mature tau. The strength of AV-1451 binding with respect to tau isoforms in various neurodegenerative disorders was: 3R + 4R tau (e.g., AD) > 3R tau (e.g., Pick disease) or 4R tau. Only minimal binding of AV-1451 to TAR DNA-binding protein-43 positive regions was detected. No binding of AV-1451 to α-synuclein was detected. "Off-target" binding was seen in vessels, iron-associated regions, substantia nigra, calcifications in the choroid plexus, and leptomeningeal melanin.

conclusionsReduced AV-1451 binding in neuritic pathology compared to neurofibrillary tangles suggests that the maturity of tau pathology may affect AV-1451 binding and suggests complexity in AV-1451 binding. Poor association of AV-1451 with tauopathies that have preferential accumulation of either 4R tau or 3R tau suggests limited clinical utility in detecting these pathologies. In contrast, for disorders associated with 3R + 4R tau, such as Alzheimer disease, AV-1451 binds tau avidly but does not completely reflect the early stage tau progression suggested by Braak neurofibrillary tangle staging. AV-1451 binding to TAR DNA-binding protein-43 or TAR DNA-binding protein-43 positive regions can be weakly positive. Clinical use of AV-1451 will require a familiarity with distinct types of "off-target" binding.

Indexed as

AutoradiographyCarbolinesPositron-Emission TomographyRadiopharmaceuticalsAgedAged, 80 and overBrainDementiaDNA-Binding ProteinsFemaleHumansMaleMiddle AgedNeurodegenerative DiseasesProtein Isoformstau Proteins7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indoleCarbolinesDNA-Binding ProteinsMAPT protein, humanProtein IsoformsRadiopharmaceuticalsTARDBP protein, humantau ProteinsAlzheimer’s diseaseAtypical Alzheimer’s diseaseAV-1451Corticobasal degenerationFrontotemporal dementiaPick DiseasePick’s diseaseProgressive supranuclear palsyTauTauopathyTDP-43

Identifiers

PMID27296779
PMCPMC4906968
OpenAlexW2426305809

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Registered trials

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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.