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

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

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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.

Original languageEnglish (US)
Pages (from-to)40
Number of pages1
JournalActa neuropathologica communications
Volume3
DOIs
StatePublished - Jul 2 2015

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Alzheimer Disease
Brain
Positron-Emission Tomography
Autoradiography
tau Proteins
Neurofibrillary Tangles
Frozen Sections
Neuroimaging
Early Diagnosis
Immunization
Binding Sites
Pathology

ASJC Scopus subject areas

  • Medicine(all)

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Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue. / Lemoine, Laetitia; Saint-Aubert, Laure; Marutle, Amelia; Antoni, Gunnar; Eriksson, Jonas P.; Ghetti, Bernardino; Okamura, Nobuyuki; Nennesmo, Inger; Gillberg, Per Göran; Nordberg, Agneta.

In: Acta neuropathologica communications, Vol. 3, 02.07.2015, p. 40.

Research output: Contribution to journalArticle

Lemoine, L, Saint-Aubert, L, Marutle, A, Antoni, G, Eriksson, JP, Ghetti, B, Okamura, N, Nennesmo, I, Gillberg, PG & Nordberg, A 2015, 'Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue', Acta neuropathologica communications, vol. 3, pp. 40. https://doi.org/10.1186/s40478-015-0220-4
Lemoine, Laetitia ; Saint-Aubert, Laure ; Marutle, Amelia ; Antoni, Gunnar ; Eriksson, Jonas P. ; Ghetti, Bernardino ; Okamura, Nobuyuki ; Nennesmo, Inger ; Gillberg, Per Göran ; Nordberg, Agneta. / Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue. In: Acta neuropathologica communications. 2015 ; Vol. 3. pp. 40.
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