eprintid: 10062789
rev_number: 22
eprint_status: archive
userid: 608
dir: disk0/10/06/27/89
datestamp: 2018-12-03 14:06:17
lastmod: 2021-10-10 22:31:39
status_changed: 2018-12-03 14:06:17
type: article
metadata_visibility: show
creators_name: Leinonen, V
creators_name: Rauramaa, T
creators_name: Johansson, J
creators_name: Bottelbergs, A
creators_name: Tesseur, I
creators_name: van der Ark, P
creators_name: Pemberton, D
creators_name: Koivisto, AM
creators_name: Jaaskelainen, JE
creators_name: Hiltunen, M
creators_name: Herukka, S-K
creators_name: Blennow, K
creators_name: Zetterberg, H
creators_name: Jokinen, P
creators_name: Rokka, J
creators_name: Heliu, S
creators_name: Haaparanta-Solin, M
creators_name: Solin, O
creators_name: Okamura, N
creators_name: Kolb, HC
creators_name: Rinne, JO
title: S-[F-18] THK-5117-PET and [C-11] PIB-PET Imaging in Idiopathic Normal Pressure Hydrocephalus in Relation to Confirmed Amyloid-beta Plaques and Tau in Brain Biopsies
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: Alzheimer’s disease, amyloid-beta, idiopathic normal pressure hydrocephalus, neuropathology, PIB, positron emission tomography, PTHK-5117, tau, contstartabstract
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: BACKGROUND:
Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer’s disease (AD) and monitor drug effects in clinical trials. S-[18F]THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[18F]THK-5117 uptake in PET with brain biopsy verified tau pathology in vivo.

OBJECTIVE:
Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[18F]THK-5117, and [11C]PIB PET against tau and amyloid lesions in brain biopsy.

METHODS:
Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical brain biopsy and CSF Aβ1 - 42, total tau, and P-tau181 measures, underwent brain MRI, [11C]PIB PET, and S-[18F]THK-5117 PET imaging.

RESULTS:
Seven patients had amyloid-β (Aβ, 4G8) plaques, two both Aβ and phosphorylated tau (Pτ, AT8) and one only Pτ in biopsy. As expected, increased brain biopsy Aβ was well associated with higher [11C]PIB uptake in PET. However, S-[18F]THK-5117 uptake did not show any statistically significant correlation with either brain biopsy Pτ or CSF P-tau181 or total tau.

CONCLUSION:
S-[18F]THK-5117 lacked clear association with neuropathologically verified tau pathology in brain biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous Aβ and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.
date: 2018
date_type: published
publisher: IOS PRESS
official_url: https://doi.org/10.3233/JAD-180071
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_manual
elements_id: 1562344
doi: 10.3233/JAD-180071
language_elements: English
lyricists_name: Zetterberg, Henrik
lyricists_id: HZETT94
actors_name: Novi, Maya
actors_id: MNOVI52
actors_role: owner
full_text_status: public
publication: Journal of Alzheimer's Disease
volume: 64
number: 1
pagerange: 171-179
pages: 9
issn: 1875-8908
citation:        Leinonen, V;    Rauramaa, T;    Johansson, J;    Bottelbergs, A;    Tesseur, I;    van der Ark, P;    Pemberton, D;                                                         ... Rinne, JO; + view all <#>        Leinonen, V;  Rauramaa, T;  Johansson, J;  Bottelbergs, A;  Tesseur, I;  van der Ark, P;  Pemberton, D;  Koivisto, AM;  Jaaskelainen, JE;  Hiltunen, M;  Herukka, S-K;  Blennow, K;  Zetterberg, H;  Jokinen, P;  Rokka, J;  Heliu, S;  Haaparanta-Solin, M;  Solin, O;  Okamura, N;  Kolb, HC;  Rinne, JO;   - view fewer <#>    (2018)    S-[F-18] THK-5117-PET and [C-11] PIB-PET Imaging in Idiopathic Normal Pressure Hydrocephalus in Relation to Confirmed Amyloid-beta Plaques and Tau in Brain Biopsies.                   Journal of Alzheimer's Disease , 64  (1)   pp. 171-179.    10.3233/JAD-180071 <https://doi.org/10.3233/JAD-180071>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10062789/3/Leinonen_Journal%20of%20Alzheimer%27s%20Disease.pdf