Rafii Michael S, Lukic Ana S, Andrews Randolph D, Brewer James, Rissman Robert A, Strother Stephen C, Wernick Miles N, Pennington Craig, Mobley William C, Ness Seth, Matthews Dawn C
Alzheimer's Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, San Diego, USA.
Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA, USA.
J Alzheimers Dis. 2017;60(2):439-450. doi: 10.3233/JAD-170390.
Adults with Down syndrome (DS) represent an enriched population for the development of Alzheimer's disease (AD), which could aid the study of therapeutic interventions, and in turn, could benefit from discoveries made in other AD populations.
Twelve non-demented adults, ages 30 to 60, with DS were enrolled in the Down Syndrome Biomarker Initiative (DSBI), a 3-year, observational, cohort study to demonstrate the feasibility of conducting AD intervention/prevention trials in adults with DS. We collected imaging data with 18F-AV-1451 tau PET, AV-45 amyloid PET, FDG PET, and volumetric MRI, as well as cognitive and functional measures and additional laboratory measures.
All amyloid negative subjects imaged were tau-negative. Among the amyloid positive subjects, three had tau in regions associated with Braak stage VI, two at stage V, and one at stage II. Amyloid and tau burden correlated with age. The MRI analysis produced two distinct volumetric patterns. The first differentiated DS from normal (NL) and AD, did not correlate with age or amyloid, and was longitudinally stable. The second pattern reflected AD-like atrophy and differentiated NL from AD. Tau PET and MRI atrophy correlated with several cognitive and functional measures.
Tau accumulation is associated with amyloid positivity and age, as well as with progressive neurodegeneration measurable using FDG and MRI. Tau correlates with cognitive decline, as do AD-specific hypometabolism and atrophy.
唐氏综合征（DS）成人患者是阿尔茨海默病（AD）发展的高危人群，这有助于研究治疗干预措施，反过来，也能从其他AD人群的研究发现中受益。
1）了解tau病理与年龄、淀粉样蛋白沉积、神经退行性变（MRI和FDG PET）以及认知和功能表现之间的关系；2）在纵向MRI中检测并区分AD特异性变化与DS特异性脑变化。
12名年龄在30至60岁之间、无痴呆的DS成人患者参加了唐氏综合征生物标志物倡议（DSBI），这是一项为期3年的观察性队列研究，旨在证明对DS成人患者进行AD干预/预防试验的可行性。我们收集了18F-AV-1451 tau PET、AV-45淀粉样蛋白PET、FDG PET和容积MRI的成像数据，以及认知和功能测量数据及其他实验室测量数据。
所有成像的淀粉样蛋白阴性受试者均为tau阴性。在淀粉样蛋白阳性受试者中，3人在与Braak VI期相关的区域有tau，2人处于V期，1人处于II期。淀粉样蛋白和tau负荷与年龄相关。MRI分析产生了两种不同的容积模式。第一种模式将DS与正常（NL）和AD区分开来，与年龄或淀粉样蛋白无关，且纵向稳定。第二种模式反映了AD样萎缩，并将NL与AD区分开来。Tau PET和MRI萎缩与多种认知和功能测量相关。
Tau积累与淀粉样蛋白阳性、年龄相关，也与使用FDG和MRI可测量的进行性神经退行性变相关。Tau与认知衰退相关，AD特异性代谢减低和萎缩也与认知衰退相关。
