A1 Journal article – refereed
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

List of Authors: Leinonen V, Rauramaa T, Johansson J, Bottelbergs A, Tesseur I, van der Ark P, Pemberton D, Koivisto AM, Jääskeläinen JE, Hiltunen M, Herukka SK, Blennow K, Zetterberg H, Jokinen P, Rokka J, Heliu S, Haaparanta-Solin M, Solin O, Okamura N, Kolb HC, Rinne JO
Publisher: IOS PRESS
Publication year: 2018
Journal: Journal of Alzheimer's Disease
Journal acronym: J ALZHEIMERS DIS
Volume number: 64
Issue number: 1
Number of pages: 9
ISSN: 1387-2877
eISSN: 1875-8908

Background: Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[F-18] THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[F-18] 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-[F-18] THK-5117, and [C-11] 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 beta(1-42), total tau, and P-tau(181) measures, underwent brain MRI, [C-11] PIB PET, and S-[F-18] THK-5117 PET imaging.Results: Seven patients had amyloid-beta(A beta, 4G8) plaques, two both A beta and phosphorylated tau (P tau, AT8) and one only P tau in biopsy. As expected, increased brain biopsy A beta was well associated with higher [C-11] PIB uptake in PET. However, S-[F-18] THK-5117 uptake did not show any statistically significant correlation with either brain biopsy P tau or CSF P-tau(181) or total tau.Conclusions: S-[F-18] 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 beta and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.

Last updated on 2019-21-08 at 22:57