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01-10-2017 | Original Paper

[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging

Authors: Marta Marquié, Michael Siao Tick Chong, Alejandro Antón-Fernández, Eline E. Verwer, Nil Sáez-Calveras, Avery C. Meltzer, Prianca Ramanan, Ana C. Amaral, Jose Gonzalez, Marc D. Normandin, Matthew P. Frosch, Teresa Gómez-Isla

Published in: Acta Neuropathologica | Issue 4/2017

Abstract

[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.

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Title: [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
Authors: Marta Marquié
Michael Siao Tick Chong
Alejandro Antón-Fernández
Eline E. Verwer
Nil Sáez-Calveras
Avery C. Meltzer
Prianca Ramanan
Ana C. Amaral
Jose Gonzalez
Marc D. Normandin
Matthew P. Frosch
Teresa Gómez-Isla
Publication date: 01-10-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 4/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-017-1740-8

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[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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