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Open Access 01-12-2015 | Research

Visualization of regional tau deposits using ³H-THK5117 in Alzheimer brain tissue

Authors: Laetitia Lemoine, Laure Saint-Aubert, Amelia Marutle, Gunnar Antoni, Jonas P Eriksson, Bernardino Ghetti, Nobuyuki Okamura, Inger Nennesmo, Per-Göran Gillberg, Agneta Nordberg

Published in: Acta Neuropathologica Communications | Issue 1/2015

Abstract

Introduction

The accumulation of neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein, starts spreading early in specific regions in the course of Alzheimer’s disease (AD), correlating with the progression of memory dysfunction. The non-invasive imaging of tau could therefore facilitate the early diagnosis of AD, differentiate it from other dementing disorders and allow evaluation of tau immunization therapy outcomes. In this study we characterized the in vitro binding properties of THK5117, a tentative radiotracer for positron emission tomography (PET) imaging of tau brain deposits.

Results

Saturation and competition binding studies of ³H-THK5117 in post-mortem AD brain tissue showed the presence of multiple binding sites. THK5117 binding was significantly higher in hippocampal (p < 0.001) and temporal (p < 0.01) tissue homogenates in AD compared to controls. Autoradiography studies with ³H-THK5117 was performed on large frozen brain sections from three AD cases who had been followed clinically and earlier undergone in vivo ¹⁸F-FDG PET investigations. The three AD cases showed distinct differences in regional THK5117 binding that were also observed in tau immunohistopathology as well as in clinical presentation. A negative correlation between in vivo ¹⁸F-FDG PET and in vitro ³H-THK5117 autoradiography was observed in two of the three AD cases.

Conclusions

This study supports that new tau PET tracers will provide further understanding on the role of tau pathology in the diversity of the clinical presentation in AD.

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Title: Visualization of regional tau deposits using 3H-THK5117 in Alzheimer brain tissue
Authors: Laetitia Lemoine
Laure Saint-Aubert
Amelia Marutle
Gunnar Antoni
Jonas P Eriksson
Bernardino Ghetti
Nobuyuki Okamura
Inger Nennesmo
Per-Göran Gillberg
Agneta Nordberg
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2015
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-015-0220-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Visualization of regional tau deposits using ³H-THK5117 in Alzheimer brain tissue

Abstract

Introduction

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Results

Conclusions

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