Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Alzheimers Dement. 2018 Jun;14(6):743-750. doi: 10.1016/j.jalz.2018.01.002. Epub 2018 Mar 1.
The objective of this study was to evaluate amyloid β (Aβ) deposition patterns in different groups of cerebral β amyloidosis: (1) nondemented with amyloid precursor protein overproduction (Down syndrome); (2) nondemented with abnormal processing of amyloid precursor protein (preclinical autosomal dominant Alzheimer disease); (3) presumed alteration in Aβ clearance with clinical symptoms (late-onset AD); and (4) presumed alterations in Aβ clearance (preclinical AD).
We performed whole-brain voxelwise comparison of cerebral Aβ between 23 Down syndrome, 10 preclinical autosomal dominant Alzheimer disease, 17 late-onset AD, and 16 preclinical AD subjects, using Pittsburgh Compound B-positron emission tomography.
We found both Down syndrome and preclinical autosomal dominant Alzheimer disease shared a distinct pattern of increased bilateral striatal and thalamic Aβ deposition compared to late-onset AD and preclinical AD.
Disorders associated with early-life alterations in amyloid precursor protein production or processing are associated with a distinct pattern of early striatal fibrillary Aβ deposition before significant cognitive impairment. A better understanding of this unique pattern could identify important mechanisms of Aβ deposition and possibly important targets for early intervention.
本研究旨在评估不同脑β淀粉样蛋白病群体中的淀粉样蛋白β(Aβ)沉积模式:(1)淀粉样前体蛋白过度产生的非痴呆(唐氏综合征);(2)淀粉样前体蛋白异常加工的非痴呆(临床前常染色体显性阿尔茨海默病);(3)有临床症状的 Aβ清除能力改变(迟发性 AD);(4)Aβ清除能力改变(临床前 AD)。
我们使用匹兹堡化合物 B-正电子发射断层扫描,对 23 例唐氏综合征、10 例临床前常染色体显性阿尔茨海默病、17 例迟发性 AD 和 16 例临床前 AD 患者的大脑 Aβ进行了全脑体素比较。
我们发现唐氏综合征和临床前常染色体显性阿尔茨海默病与迟发性 AD 和临床前 AD 相比,双侧纹状体和丘脑 Aβ沉积均有明显增加。
与生命早期淀粉样前体蛋白产生或加工改变相关的疾病与认知功能损害前明显的纹状体纤维状 Aβ沉积有明显的模式有关。更好地了解这种独特的模式可以确定 Aβ沉积的重要机制,并可能确定早期干预的重要靶点。