Abstract
IntroductionAdults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. MethodsForty-nine adults with DS aged 25–65 underwent positron emission tomography with Pittsburgh compound–B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. ResultsAbnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. DiscussionPIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial.
Highlights
This study found that Pittsburgh compound–B (PIB) binding in the brains of adults with Down syndrome (DS) becomes evident from around age 40 years and increases in spatial extent in an age-dependent manner
The first brain region to become PIB-positive was the striatum, followed by PIB binding in the rostral prefrontal-cinguloparietal regions, caudal frontal, rostral temporal, primary sensorimotor and occipital, and mediotemporal regions and the rest of the basal ganglia
A critical finding of the study was that evidence of abnormal PIB binding was strongly associated with a clinical diagnosis of “dementia” or “cognitive decline” (65% of cases) without evidence of a substantial time window between the development of abnormal PIB binding and cognitive decline
Summary
Adults with Down syndrome (DS) invariably develop senile plaques, composed of b-amyloid peptide (Ab), indistinguishable from the histopathology of sporadic Alzheimer’s disease (AD) [1,2], and have a high risk for the development of early onset dementia [3] with estimated age-specific. Scan 0–90 min after injection, BPND estimated with cerebellum as reference region, region-specific positive-binding thresholds. Scan 40–60 min after injection, SUVR using cerebellum reference region; region-specific positive-binding thresholds. Scan 50–70 min after injection, SUVR using subcortical white matter and cerebellum reference region, region-specific positive-binding thresholds. Scan 100–120 min after injection, SUVR using cerebellum reference region, composite region positive-binding threshold precursor protein gene, located on chromosome 21. In younger individuals, imaging has generally shown an absence of amyloid binding, some single isolated cases have been reported with focal striatal binding [12,13,14] These previous studies have used large anatomic regions of interest (ROI) in relatively small numbers of participants, making a more fine-grained and systematic study of amyloid accumulation across different brain areas highly desirable. This report, characterizes in detail the evolution of PIB binding in cortical and subcortical regions of the DS brain
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