[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
Open accessAbstract
[F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. We studied the correlation of autoradiographic binding patterns of [F-18]-AV-1451 and the stereotypical spatiotemporal pattern of progression of NFTs using legacy postmortem brain samples representing different Braak NFT stages (I-VI). We performed [F-18]-AV-1451 phosphor-screen autoradiography and quantitative tau measurements (stereologically based NFT counts and biochemical analysis of tau pathology) in three brain regions (entorhinal cortex, superior temporal sulcus and visual cortex) in a total of 22 cases: low Braak (I-II, n = 6), intermediate Braak (III-IV, n = 7) and high Braak (V-VI, n = 9). Strong and selective [F-18]-AV-1451 binding was detected in all tangle-containing regions matching precisely the observed pattern of PHF-tau immunostaining across the different Braak stages. As expected, no signal was detected in the white matter or other non-tangle containing regions. Quantification of [F-18]-AV-1451 binding was very significantly correlated with the number of NFTs present in each brain region and with the total tau and phospho-tau content as reported by Western blot and ELISA. [F-18]-AV-1451 is a promising biomarker for in vivo quantification of brain tau burden in AD. Neuroimaging-pathologic studies conducted on postmortem material from individuals imaged while alive are now needed to confirm these observations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Flortaucipir binding correlates with Braak neurofibrillary tangles stage.
“In vivo imaging to autopsy comparisons also indicates specific binding of flortaucipir to PHF tangles [23] and correlation with the Braak neurofibrillary tangles stage [129].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [129]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 36 · Cited by 109
Research works printed but not linked: 20
- [4]Cairns NJ Bigio EH Mackenzie IR Neumann M Lee VM Hatanpaa KJ White CL 3rd Schneider JA Grinberg LT Halliday G Duyckaerts C Lowe JS Holm IE Tolnay M Okamoto K Yokoo H Murayama S Woulfe J Munoz DG Dickson DW Ince PG Trojanowski JQ Mann DM Consortium for Frontotemporal Lobar D 2007 Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration Acta neuropathologica 114 1 5 22 10.1007/s00401-007-0237-2 17579875 PMC2827877 · DOI · Paper page
- [7]Cho H Choi JY Hwang MS Lee JH Kim YJ Lee HM Lyoo CH Ryu YH Lee MS 2016 Tau PET in Alzheimer disease and mild cognitive impairment Neurology 87 4 375 383 10.1212/WNL.0000000000002892 27358341 · DOI
- [8]Gordon BA Friedrichsen K Brier M Blazey T Su Y Christensen J Aldea P McConathy J Holtzman DM Cairns NJ Morris JC Fagan AM Ances BM Benzinger TL 2016 The relationship between cerebrospinal fluid markers of Alzheimer pathology and positron emission tomography tau imaging Brain: a journal of neurology 139 Pt 8 2249 2260 10.1093/brain/aww139 27286736 PMC4958902 · DOI · Paper page
- [10]Johnson KA Schultz A Betensky RA Becker JA Sepulcre J Rentz D Mormino E Chhatwal J Amariglio R Papp K Marshall G Albers M Mauro S Pepin L Alverio J Judge K Philiossaint M Shoup T Yokell D Dickerson B Gomez-Isla T Hyman B Vasdev N Sperling R 2016 Tau positron emission tomographic imaging in aging and early Alzheimer disease Annals of neurology 79 1 110 119 10.1002/ana.24546 26505746 PMC4738026 · DOI · Paper page
- [11]Lowe VJ Curran G Fang P Liesinger AM Josephs KA Parisi JE Kantarci K Boeve BF Pandey MK Bruinsma T Knopman DS Jones DT Petrucelli L Cook CN Graff-Radford NR Dickson DW Petersen RC Jack CR Jr Murray ME 2016 An autoradiographic evaluation of AV-1451 Tau PET in dementia Acta neuropathologica communications 4 1 58 10.1186/s40478-016-0315-6 27296779 PMC4906968 · DOI · Paper page
- [12]Marquie M Normandin MD Meltzer AC Siao Tick Chong M Andrea NV Anton-Fernandez A Klunk WE Mathis CA Ikonomovic MD Debnath M Bien EA Vanderburg CR Costantino I Makaretz S DeVos SL Oakley DH Gomperts SN Growdon JH Domoto-Reilly K Lucente D Dickerson BC Frosch MP Hyman BT Johnson KA Gomez-Isla T 2017 Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies Annals of neurology 81 1 117 128 10.1002/ana.24844 27997036 PMC5319193 · DOI · Paper page
- [13]Marquie M Normandin MD Vanderburg CR Costantino IM Bien EA Rycyna LG Klunk WE Mathis CA Ikonomovic MD Debnath ML Vasdev N Dickerson BC Gomperts SN Growdon JH Johnson KA Frosch MP Hyman BT Gomez-Isla T 2015 Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue Annals of neurology 78 5 787 800 10.1002/ana.24517 26344059 PMC4900162 · DOI · Paper page
- [14]Mattsson N Rosen E Hansson O Andreasen N Parnetti L Jonsson M Herukka SK van der Flier WM Blankenstein MA Ewers M Rich K Kaiser E Verbeek MM Olde Rikkert M Tsolaki M Mulugeta E Aarsland D Visser PJ Schroder J Marcusson J de Leon M Hampel H Scheltens P Wallin A Eriksdotter-Jonhagen M Minthon L Winblad B Blennow K Zetterberg H 2012 Age and diagnostic performance of Alzheimer disease CSF biomarkers Neurology 78 7 468 476 10.1212/WNL.0b013e3182477eed 22302554 PMC3280049 · DOI
- [15]McKeith IG 2006 Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop Journal of Alzheimer’s disease: JAD 9 3 Suppl 417 423 16914880
- [16]Mirra SS Heyman A McKeel D Sumi SM Crain BJ Brownlee LM Vogel FS Hughes JP van Belle G Berg L 1991 The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease Neurology 41 4 479 486 2011243
- [19]Pontecorvo MJ Devous MD Sr Navitsky M Lu M Salloway S Schaerf FW Jennings D Arora AK McGeehan A Lim NC Xiong H Joshi AD Siderowf A Mintun MA investigators FA-A 2017 Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition Brain: a journal of neurology 10.1093/brain/aww334 PMC5382945 28077397 · DOI · Paper page
- [20]Qian J Hyman BT Betensky RA 2017 Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms: Modeling Using an Autopsy Cohort and Application to Clinical Trial Design JAMA neurology 10.1001/jamaneurol.2016.5953 PMC5547572 28288263 · DOI
- [21]Riley KP Snowdon DA Markesbery WR 2002 Alzheimer’s neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study Annals of neurology 51 5 567 577 10.1002/ana.10161 12112102 · DOI
- [22]Rosen C Hansson O Blennow K Zetterberg H 2013 Fluid biomarkers in Alzheimer’s disease - current concepts Molecular neurodegeneration 8 20 10.1186/1750-1326-8-20 23800368 PMC3691925 · DOI
- [23]Rowe CC Ng S Ackermann U Gong SJ Pike K Savage G Cowie TF Dickinson KL Maruff P Darby D Smith C Woodward M Merory J Tochon-Danguy H O’Keefe G Klunk WE Mathis CA Price JC Masters CL Villemagne VL 2007 Imaging beta-amyloid burden in aging and dementia Neurology 68 20 1718 1725 10.1212/01.wnl.0000261919.22630.ea 17502554 · DOI · Paper page
- [24]Sander K Lashley T Gami P Gendron T Lythgoe MF Rohrer JD Schott JM Revesz T Fox NC Arstad E 2016 Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer’s disease, primary tauopathies, and other dementias Alzheimer’s & dementia: the journal of the Alzheimer’s Association 12 11 1116 1124 10.1016/j.jalz.2016.01.003 26892233 · DOI · Paper page
- [26]Schwarz AJ Yu P Miller BB Shcherbinin S Dickson J Navitsky M Joshi AD Devous MD Sr Mintun MS 2016 Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages Brain: a journal of neurology 10.1093/brain/aww023 26936940 · DOI · Paper page
- [28]Villemagne VL Ong K Mulligan RS Holl G Pejoska S Jones G O’Keefe G Ackerman U Tochon-Danguy H Chan JG Reininger CB Fels L Putz B Rohde B Masters CL Rowe CC 2011 Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias Journal of nuclear medicine: official publication, Society of Nuclear Medicine 52 8 1210 1217 10.2967/jnumed.111.089730 21764791 · DOI
- [29]Vonsattel JP Del Amaya MP Keller CE 2008 Twenty-first century brain banking. Processing brains for research: the Columbia University methods Acta neuropathologica 115 5 509 532 10.1007/s00401-007-0311-9 17985145 PMC2292479 · DOI
- [30]Wang L Benzinger TL Su Y Christensen J Friedrichsen K Aldea P McConathy J Cairns NJ Fagan AM Morris JC Ances BM 2016 Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between beta-Amyloid and Tauopathy JAMA neurology 10.1001/jamaneurol.2016.2078 PMC5237382 27454922 · DOI
- Authors
- Marquié, M., Siao Tick Chong, M., Antón-Fernández, A., Verwer, E. E., Sáez-Calveras, N., Meltzer, A. C., Ramanan, P., Amaral, A. C., Gonzalez, J., Normandin, M. D., Frosch, M. P., & Gómez-Isla, T.
- Affiliations
- Massachusetts General Hospital (US)
- Gordon Center for Medical Imaging (US)
- Venue
- Acta Neuropathologica
- Published
- 2017-06-13
- Volume
- 134
- Issue
- 4
- Pages
- 619-628
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC5772971
- OpenAlex
- W2625608650
- Cited by
- 109
- References
- 36
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 10 · 2023: 8 · 2022: 11 · 2021: 14 · 2020: 15 · 2019: 14 · 2018: 11 · 2017: 5
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- ASISA Foundation
- National Institute of Neurological Disorders and Stroke (U01NS086659)
- National Institute of Mental Health (R01MH100350)
- Ministry of Economy and Competitiveness - State Secretariat for Research, Development and Innovation of Spain (SAF 2015-66603-P)
- National Institute on Aging (AG005134, AG036694)
- Alzheimer's Disease Research Center
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- tau PET tracers, neurofibrillary tangles, Braak staging, Alzheimer's disease, tau burden, entorhinal cortex, superior temporal sulcus, visual cortex, phosphorylated tau
- MeSH terms
- Aged, Aged, 80 and over, Autoradiography, Brain, Carbolines, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Male, Middle Aged, Phosphorylation, Severity of Illness Index, Blotting, Western, Neurofibrillary Tangles, tau Proteins, Radiopharmaceuticals, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
