Estimation of amyloid distribution by [18F]flutemetamol PET predicts the neuropathological phase of amyloid ?-protein deposition.

ABSTRACT: The deposition of the amyloid ?-protein (A?) in senile plaques is one of the histopathological hallmarks of Alzheimer's disease (AD). A?-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological A?-phases with amyloid PET imaging. To address this question we reassessed 97 cases of the end-of-life study cohort of the phase 3 [18F]flutemetamol trial (ClinicalTrials.gov identifiers NCT01165554, and NCT02090855) by combining the standardized uptake value ratios (SUVRs) with pons as reference region for cortical and caudate nucleus-related [18F]flutemetamol-retention. We tested them for their prediction of the neuropathological pattern found at autopsy. By defining threshold levels for cortical and caudate nucleus SUVRs we could distinguish different levels of [18F]flutemetamol uptake termed PET-A? phase estimates. When comparing these PET-A? phase estimates with the neuropathological A?-phases we found that PET-A? phase estimate 0 corresponded with A?-phases 0-2, 1 with A?-phase 3, 2 with A?-phase 4, and 3 with A?-phase 5. Classification using the PET-A? phase estimates predicted the correct A?-phase in 72.16% of the cases studied here. Bootstrap analysis was used to confirm the robustness of the estimates around this association. When allowing a range of?±?1 phase for a given A?-phase correct classification was given in 96.91% of the cases. In doing so, we provide a novel method to convert SUVR-levels into PET-A? phase estimates that can be easily translated into neuropathological phases of A?-deposition. This method allows direct conclusions about the pathological distribution of amyloid plaques (A?-phases) in vivo. Accordingly, this method may be ideally suited to detect early preclinical AD-patients, to follow them with disease progression, and to provide a more precise prognosis for them based on the knowledge about the underlying pathological phase of the disease.

SUBMITTER: Thal DR 

PROVIDER: S-EPMC6132944 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature