Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA, USA.
Department of Biostatistics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA, USA.
Neurobiol Aging. 2019 Jan;73:171-176. doi: 10.1016/j.neurobiolaging.2018.09.030. Epub 2018 Sep 27.
Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([C]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 [C]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 [C]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.
唐氏综合征(DS)使个体易患早发性阿尔茨海默病(AD)。使用匹兹堡化合物 B([C]PiB),已经报道了纹状体淀粉样β(Aβ)的模式,其相对于新皮层结合升高,类似于非痴呆常染色体显性 AD 突变携带者。然而,当与非痴呆老年(NDE)人群相比,在非痴呆 DS 人群中,纹状体和新皮层[C]PiB 保留的变化是否随时间而不同尚不清楚。这项工作的目的是评估与 NDE 队列相比,在非痴呆 DS 中 Aβ的轨迹随时间的纵向变化。使用线性混合效应模型,使用时间、队列和时间-队列相互作用的固定效应以及受试者作为随机效应,探索了前腹侧纹状体(AVS)、额叶皮层和楔前叶[C]PiB 保留的区域轨迹。观察到所有 3 个感兴趣区域的 DS 和 NDE 队列轨迹之间存在显著差异(p<0.05),与 NDE 队列相比,DS 队列在 AVS 中的积累速度更快,而在额叶皮层和楔前叶中的积累速度更慢。这些数据通过证明与 NDE 受试者相比,DS 个体在 AVS 中也可能以更快的速度积累 Aβ,补充了先前报道的早期纹状体沉积的独特模式,这在散发性 AD 中通常不会见到。