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THE ASSOCIATION BETWEEN AB AND TAU ACCUMULATIONS AND ITS INFLUENCE ON CLINICAL FEATURES IN AGING AND ALZHEIMER’S DISEASE SPECTRUM BRAINS: [11C]PBB3 PET STUDY

      Background

      Senile plaques and fibrillary tau inclusions are neuropathological hallmarks of Alzheimer’s disease (AD). Recent neuroimaging and neuropathological studies have revealed that proteinopathies represented by amyloid-β (Aβ) and tau accumulations may occur independently and concurrently as exemplified by primary age-related tauopathy and AD, respectively. To elucidate interactions between Aβ and tau accumulations and its influence on clinical features, we performed a cross-sectional positron emission tomography (PET) study in cognitively healthy and impaired individuals.

      Methods

      Participants were 20 patients with AD, 17 patients with mild cognitive impairment (MCI), 24 age-matched healthy controls (oHCs) and 10 young HCs. Parametric [11C]PBB3-, [11C]PiB- and [18F]FDG-PET images were genrated for estimating regional Aβ, tau and brain glucose metabolism, respectively, by voxel-based calculation of standardized uptake value ratio (SUVR) to the cerebellum at 30-50 minutes, 50-70 minutes and 30-60 minutes after radiotracer injections, respectively. We also performed three-dimensional T1-weighted MRI and estimated whole grey matter volume for each subject.

      Results

      All AD patients, 10 of 17 MCI patients, and 3 of 24 oHCs were classified as PiB(+), and others were classified as PiB(-) by visual assessment of [11C]PiB SUVR images. PBB3(+) tau deposits were observed in medial temporal regions including the hippocampus of a subset of PiB(-) oHCs, and this was associated with subclinical memory declines. Self-expansion of tau deposition to restricted areas without Aβ was also demonstrated in these and PiB(-) MCI subjects. PBB3(+) tau spread to Aβ-rich areas in PiB(+) oHCs and MCI subjects, and was further expanded to widespread neocortical regions in AD patients. In PiB(+) MCI and AD groups, dementia scales and whole grey matter volumes were correlated with tau but not Aβ deposits, and frontal dysfunctions were associated with frontal tau accumulation. Additionally, hypometabolic areas detected by [18F]FDG-PET spread in transition from oHC to AD in a pattern following expansion of tau pathologies.

      Conclusions

      The present study indicated that Aβ deposition promotes tau propagation, and also supports Aβ-independent and -dependent pathways of tau pathogenesis that can be pursued by PET, in close relation to cognitions of healthy and diseased elderly individuals.