Abstract
Although clinical routine focuses on dichotomous and visual interpretation of amyloid PET, regional image assessment in research settings may yield additional opportunities. Understanding the regional-temporal evolution of amyloid pathology may enable earlier identification of subjects in the Alzheimer Disease pathologic continuum, as well as a finer-grained assessment of pathology beyond traditional dichotomous measures. This review summarizes current research in the detection of regional amyloid deposition patterns and its potential for staging amyloid pathology. Pathology studies, cross-sectional and longitudinal PET-only studies, and comparative PET and autopsy studies are included. Despite certain differences, cortical deposition generally precedes striatal pathology, and in PET-only studies, medial cortical regions are seen to accumulate amyloid earlier than lateral regions. Based on regional amyloid PET, multiple studies have developed and implemented models for staging amyloid pathology that could improve subject selection into secondary prevention trials and visual assessment in clinical routine.
Highlights
PET imaging allows the visualization and quantification of amyloid-b (Ab) plaques, a key physiopathologic hallmark for the placement of individuals along the Alzheimer disease (AD) continuum [1]
The diversity of approaches reveals that a universally applicable regional amyloid staging strategy requires consideration of the methodologic discrepancies discussed in this review
The quest to determine the most likely temporal order of regional amyloid deposition in AD benefits from studies examining the diverse range of cohorts of ever-increasing size and heterogeneity
Summary
PET imaging allows the visualization and quantification of amyloid-b (Ab) plaques, a key physiopathologic hallmark for the placement of individuals along the Alzheimer disease (AD) continuum [1]. Recent reports suggest that regional patterns can be used to identify the earliest signs of amyloid pathology and may indicate potential for conversion to dementia in later stages of the pathologic process In this context, this article critically synthesizes key research in the field of regional amyloid analysis, with the objective of advancing the overall understanding of amyloid PET’s role in the evaluation of subjects in the earlier phases of the AD spectrum. Braak and Braak [20] evaluated the progressive topology and density of amyloid deposits in an analysis of 83 postmortem brains from demented and nondemented elderly patients Based on both frequency and density of plaques, 3 stages of amyloid deposition were described, starting with deposits in basal portions of the frontal, temporal, and occipital lobes, followed by medium-density deposits throughout cortical association areas and white matter, as well as mild involvement of the hippocampus, and ending with inclusion of the sensorimotor
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