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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Alzheimer's disease

amyloid-beta

idiopathic normal pressure hydrocephalus

neuropathology

PIB

positron-emission-tomography

alzheimers-disease

follow-up

biomarkers

csf

pathology

Neurosciences & Neurology

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