TY  - JOUR
EP  - 179
AV  - public
Y1  - 2018///
TI  - 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
KW  - Alzheimer?s disease
KW  -  amyloid-beta
KW  -  idiopathic normal pressure hydrocephalus
KW  -  neuropathology
KW  -  PIB
KW  -  positron emission tomography
KW  -  PTHK-5117
KW  -  tau
KW  -  contstartabstract
PB  - IOS PRESS
ID  - discovery10062789
N2  - 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 A?1 - 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-? (A?, 4G8) plaques, two both A? and phosphorylated tau (P?, AT8) and one only P? in biopsy. As expected, increased brain biopsy A? 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 P? 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 A? and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
IS  - 1
VL  - 64
SP  - 171
A1  - Leinonen, V
A1  - Rauramaa, T
A1  - Johansson, J
A1  - Bottelbergs, A
A1  - Tesseur, I
A1  - van der Ark, P
A1  - Pemberton, D
A1  - Koivisto, AM
A1  - Jaaskelainen, JE
A1  - Hiltunen, M
A1  - Herukka, S-K
A1  - Blennow, K
A1  - Zetterberg, H
A1  - Jokinen, P
A1  - Rokka, J
A1  - Heliu, S
A1  - Haaparanta-Solin, M
A1  - Solin, O
A1  - Okamura, N
A1  - Kolb, HC
A1  - Rinne, JO
JF  - Journal of Alzheimer's Disease
SN  - 1875-8908
UR  - https://doi.org/10.3233/JAD-180071
ER  -