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Acta Neuropathol Commun. 2015 Jul 2;3:40. doi: 10.1186/s40478-015-0220-4.

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

Author information

1
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum, 5th floor, Stockholm, S-14157, Sweden.
2
Preclinical PET Platform, Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden.
3
PET Centre, Centre for Medical Imaging, Uppsala University Hospital, Uppsala, Sweden.
4
Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
5
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
6
Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
7
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Karolinska Institutet, Novum, 5th floor, Stockholm, S-14157, Sweden. Agneta.K.Nordberg@ki.se.
8
Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. Agneta.K.Nordberg@ki.se.

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 (3)H-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 (3)H-THK5117 was performed on large frozen brain sections from three AD cases who had been followed clinically and earlier undergone in vivo (18)F-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 (18)F-FDG PET and in vitro (3)H-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.

PMID:
26134112
PMCID:
PMC4489196
DOI:
10.1186/s40478-015-0220-4
[Indexed for MEDLINE]
Free PMC Article

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