Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis.
Forty-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.
Abnormal 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.
PIB 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.