Tudorascu, Dana LAnderson, Stewart JMinhas, Davneet SYu, ZhemingComer, DianeLao, PatrickHartley, SiganLaymon, Charles MSnitz, Beth ELopresti, Brian JJohnson, SterlingPrice, Julie CMathis, Chester AAizenstein, Howard JKlunk, William EHanden, Benjamin LChristian, Brad TCohen, Ann D
Summary
Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD) through accumulation of amyloid-beta throughout their lifespan. Using Pittsburgh Compound B ([11C]PiB), researchers have identified a pattern of striatal amyloid beta (Aβ) accumulation in DS brains similar to that of elderly AD mutation carriers who are not experiencing dementia (NDE). This research assesses longitudinal changes in trajectories of Aβ in those with a DS and a cohort of NDE without DS. Significant differences between DS and NDE cohort trajectories for all 3 highlighted regions of interest in the brain. These data add to the previously reported distinct pattern of early deposition not commonly seen in sporadic AD. It does so by demonstrating that individuals with DS may also accumulate Aβ at a rate faster than NDE subjects.
Abstract
Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([11C]PiB), a pattern of striatal amyloid beta (Aβ) that is elevated relative to neocortical binding has been reported, similar to that of nondemented autosomal dominant AD mutation carriers. However, it is not known whether changes in striatal and neocortical [11C]PiB retention differ over time in a nondemented DS population when compared to changes in a nondemented elderly (NDE) population. The purpose of this work was to assess longitudinal changes in trajectories of Aβ in a nondemented DS compared to an NDE cohort. The regional trajectories for anterior ventral striatum (AVS), frontal cortex, and precuneus [11C]PiB retention were explored over time using linear mixed effects models with fixed effects of time, cohort, and time-by-cohort interactions and subject as random effects. Significant differences between DS and NDE cohort trajectories for all 3 region of interests were observed (p < 0.05), with the DS cohort showing a faster accumulation in the AVS and slower accumulation in the frontal cortex and precuneus compared to the NDE cohort. These data add to the previously reported distinct pattern of early striatal deposition not commonly seen in sporadic AD by demonstrating that individuals with DS may also accumulate Aβ at a rate faster in the AVS when compared to NDE subjects.
Conditions
Alzheimer Disease