Biopathological Significance of Early-Phase Amyloid Imaging in the Spectrum of Alzheimer's Disease

Abstract

Background: Amyloid imaging with positron emission tomography (PET) often comes with glucose metabolic imaging in diagnosis of Alzheimer's disease (AD).

Objective: The present purpose was to explore the clinical valence of early amyloid-β (Aβ) PET scans to determine whether they could substitute for other imaging biomarkers (early and delayed Aβ images of 11C-Pittsburgh compound B (PIB) and 18F-fluorodeoxyglucose (FDG) images) in the AD spectrum.

Methods: Thirty healthy control subjects, 20 patients with mild cognitive impairment, and 45 patients with AD underwent 11C-PIB and 18F- FDG PET. Image analyses were performed with three-dimensional stereotactic surface projection and Brodmann's area regions-of-interest methods. Since early accumulation of PIB (ePIB) reflects blood flow, we classified all subjects according to the level of ePIB in the posterior cingulate gyrus, precuneus, and lateral parietal cortex. We compared the PET parameters (ePIB, delayed-phase PIB accumulation or dPIB, FDG) to determine whether ePIB-based categorization reflected Aβ deposition in a Braak stage-related fashion.

Results: We found that ePIB images were similar to 18F-FDG images and that the progress of Aβ deposition deduced from the reduction in ePIB index was similar to the pathological progress of Braak staging. A decrease in the ePIB level in the posterior cingulate gyrus, precuneus, and parietal cortex was shown to correspond to greater and wider Aβ deposition in the medial frontal, anterior, and posterior cingulate gyri.

Conclusions: The early-phase 11C-PIB index can be an alternative to the neurogenerative markers of glucose hypometabolism and reflects the Braak stage of Aβ deposition in the living AD brain.

Keywords: 11C-PIB; 18F-FDG; Alzheimer’s disease; Braak stage; amyloid; glucose; positron emission tomography.