S-[18F]THK-5117-PET and [11C]PIB-PET Imaging in Idiopathic Normal Pressure Hydrocephalus in Relation to Confirmed Amyloid-β Plaques and Tau in Brain Biopsies
| Autor: | Ville Leinonen, Anne M. Koivisto, Johanna Rokka, Juha E. Jääskeläinen, Juha O. Rinne, Astrid Bottelbergs, Olof Solin, Ina Tesseur, Nobuyuki Okamura, Semi Helin, Peter van der Ark, Henrik Zetterberg, Pekka Jokinen, Sanna-Kaisa Herukka, Merja Haaparanta-Solin, Jarkko Johansson, Mikko Hiltunen, Kaj Blennow, Hartmuth C. Kolb, Tuomas Rauramaa, Darrel J. Pemberton |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Amyloid Amyloid beta Plaque Amyloid tau Proteins Neuropathology 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid In vivo Biopsy Humans Medicine Aged Aged 80 and over Brain Mapping Aniline Compounds biology medicine.diagnostic_test business.industry General Neuroscience Brain biopsy Brain General Medicine Middle Aged Magnetic Resonance Imaging Hydrocephalus Normal Pressure Thiazoles Psychiatry and Mental health Clinical Psychology 030104 developmental biology Positron emission tomography Positron-Emission Tomography Quinolines biology.protein Female Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 64:171-179 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-180071 |
| Popis: | 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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