Alzheimer’s disease (AD) is the most common neurodegenerative disorder
pathologically characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles.
The aggregation of Aβ precedes tau pathologies in AD; however, the causal relation
between the two pathologies and the mechanisms by which aggregated forms of Aβ
contribute to cortical thinning are not fully understood. We proposed quantitative Aβ-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 Aβ deposition and there are areas that are relatively independent from Aβ deposition where pathologies
other than Aβ (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 Aβ-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 Aβ deposition such as Aβ deposition after cortical thinning; cortical thinning after Aβ
deposition, or concurrent Aβ deposition and cortical thinning, we identified three types of relationships between cortical
thinning and Aβ deposition: (1) Aβ-associated cortical thinning; (2) Aβ-independent cortical thinning; and (3) Aβ deposition
only without cortical thinning. Taken together, these findings suggest that Aβ-weighted cortical thickness values can
be used as an objective biomarker of structural changes caused by amyloid pathology in the brain.
Keywords: Alzheimer’s disease, Amyloid beta, amyloid imaging, Aβ-weighted cortical thickness, magnetic resonance imaging,
mild cognitive impairment, normal cognition, tau.
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