@article{discovery10062789,
          number = {1},
            year = {2018},
         journal = {Journal of Alzheimer's Disease},
       publisher = {IOS PRESS},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
           pages = {171--179},
           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},
          volume = {64},
        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 A{\ensuremath{\beta}}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-{\ensuremath{\beta}} (A{\ensuremath{\beta}}, 4G8) plaques, two both A{\ensuremath{\beta}} and phosphorylated tau (P{\ensuremath{\tau}}, AT8) and one only P{\ensuremath{\tau}} in biopsy. As expected, increased brain biopsy A{\ensuremath{\beta}} 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{\ensuremath{\tau}} 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{\ensuremath{\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.},
        keywords = {Alzheimer's disease, amyloid-beta, idiopathic normal pressure hydrocephalus, neuropathology, PIB, positron emission tomography, PTHK-5117, tau, contstartabstract},
            issn = {1875-8908},
             url = {https://doi.org/10.3233/JAD-180071},
          author = {Leinonen, V and Rauramaa, T and Johansson, J and Bottelbergs, A and Tesseur, I and van der Ark, P and Pemberton, D and Koivisto, AM and Jaaskelainen, JE and Hiltunen, M and Herukka, S-K and Blennow, K and Zetterberg, H and Jokinen, P and Rokka, J and Heliu, S and Haaparanta-Solin, M and Solin, O and Okamura, N and Kolb, HC and Rinne, JO}
}