Amyloid Beta-Weighted Cortical Thickness: A New Imaging Biomarker in Alzheimer's Disease

초록

Alzheimer's disease (AD) is the most common neurodegenerative disorder pathologically characterized by amyloid-beta (A beta) plaques and neurofibrillary tangles. The aggregation of A beta precedes tau pathologies in AD; however, the causal relation between the two pathologies and the mechanisms by which aggregated forms of A beta contribute to cortical thinning are not fully understood. We proposed quantitative A beta-weighted cortical thickness analysis to investigate the regional relationship between cortical thinning and amyloid plaque deposition using magnetic resonance (MR) and Pittsburg Compound B (PiB) positron emission tomography (PET) images in patients with AD, mild cognitive impairment (MCI), and subjects with normal cognition. We hypothesized that there are cortical areas that have prominent changes associated with A beta deposition and there are areas that are relatively independent from A beta deposition where pathologies other than A beta (such as tau) are predominant. The study was performed using MRI and PiB PET data from the Alzheimer's Disease Neuroimaging Initiative. We measured accuracy of classification models in three different pairs of groups comparing AD, MCI, and normal cognition. Classification models that used A beta-weighted cortical thickness were not inferior to classification models that used only cortical thickness or amyloid deposition. In addition, based on timing of changes in cortical thinning and A beta deposition such as A beta deposition after cortical thinning; cortical thinning after A beta deposition, or concurrent A beta deposition and cortical thinning, we identified three types of relationships between cortical thinning and A beta deposition: (1) A beta-associated cortical thinning; (2) A beta-independent cortical thinning; and (3) A beta deposition only without cortical thinning. Taken together, these findings suggest that A beta-weighted cortical thickness values can be used as an objective biomarker of structural changes caused by amyloid pathology in the brain.

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