Abstract
PurposeTo assess the in vivo whole-brain relationship between uptake of [18F]THK-5351 on PET and cortical atrophy on structural MRI according to the presence and severity of Alzheimer’s disease (AD).Materials and methodsSixty-five participants (21 normal controls, 32 mild cognitive impairment [MCI] subjects, and 12 AD patients) were enrolled from a prospective multicenter clinical trial (NCT02656498). Structural MRI and [18F]THK-5351 PET were performed within a 2-month interval. Cortical volume and standardized uptake value ratios (SUVR) were calculated from MRI and PET images, respectively, for 35 FreeSurfer-derived cortical regions. Pearson’s correlation coefficients between SUVR and cortical volume were calculated for the same regions, and correlated regions were compared according to disease severity and β-amyloid PET positivity.ResultsNo significantly correlated regions were found in the normal controls. Negative correlations between SUVR and cortical volume were found in the MCI and AD groups, mainly in limbic locations in MCI and isocortical locations in AD. The AD group exhibited stronger correlations (r = −0.576–0.781) than the MCI group (r = 0.368–0.571). Hippocampal atrophy did not show any correlation with SUVR in the β-amyloid PET-negative group, but negatively correlated with SUVR (r = −0.494, P = .012) in the β-amyloid PET-positive group.ConclusionsRegional THK-5351 uptake correlated more strongly with cortical atrophy in AD compared with MCI, thereby demonstrating a close relationship between the neuro-pathologic process and cortical atrophy. Hippocampal atrophy was associated with both β-amyloid and THK-5351 uptake, possibly reflecting an interaction between β-amyloid and tau deposition in the neurodegeneration process.
Highlights
Ever since Braak and Braak demonstrated the neuropathological staging of Alzheimer’s disease (AD) with tau aggregates [1, 2], the noninvasive measurement of tau propagation has been of great clinical interest
Negative correlations between standardized uptake value ratios (SUVR) and cortical volume were found in the mild cognitive impairment (MCI) and AD groups, mainly in limbic locations in MCI and isocortical locations in AD
Regional THK-5351 uptake correlated more strongly with cortical atrophy in AD compared with MCI, thereby demonstrating a close relationship between the neuro-pathologic process and cortical atrophy
Summary
Ever since Braak and Braak demonstrated the neuropathological staging of Alzheimer’s disease (AD) with tau aggregates [1, 2], the noninvasive measurement of tau propagation has been of great clinical interest. The progression of tau aggregates observed in an autopsy study seems to match the patterns of cortical atrophy on MRI [5], with a high tau burden being associated with greater cortical loss in medial and lateral temporal lobes. A similar finding was shown using a different radioactive tracer, AV-1451, with the AD cortical signature regions of medial, inferior, and lateral temporal lobes, as well as the inferior parietal lobule, exhibiting significant correlations with PET uptake [7]. Studies demonstrating the relationship between tau PET binding and regional atrophy across the AD spectrum, including in mild cognitive impairment (MCI), are limited becasue the subject groups have generally been confined to AD patients and normal controls (NCs). The association may be modified by the β-amyloid status of patients, with increased β-amyloid in the cerebral spinal fluid (CSF) showing an association with hippocampal atrophy [7], this has not been demonstrated using noninvasive imaging modalities
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