Doran Eric, Keator David, Head Elizabeth, Phelan Michael J, Kim Ron, Totoiu Minodora, Barrio Jorge R, Small Gary W, Potkin Steven G, Lott Ira T
Department of Pediatrics, University of California, Irvine Medical Center, Orange, CA, USA.
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
J Alzheimers Dis. 2017;56(2):459-470. doi: 10.3233/JAD-160836.
Overexpression of the amyloid precursor protein (APP) gene on chromosome 21 in Down syndrome (DS) has been linked to increased brain amyloid levels and early-onset Alzheimer's disease (AD). An elderly man with phenotypic DS and partial trisomy of chromosome 21 (PT21) lacked triplication of APP affording an opportunity to study the role of this gene in the pathogenesis of dementia. Multidisciplinary studies between ages 66-72 years comprised neuropsychological testing, independent neurological exams, amyloid PET imaging with 11C-Pittsburgh compound-B (PiB), plasma amyloid-β (Aβ) measurements, and a brain autopsy examination. The clinical phenotype was typical for DS and his intellectual disability was mild in severity. His serial neuropsychological test scores showed less than a 3% decline as compared to high functioning individuals with DS who developed dementia wherein the scores declined 17-28% per year. No dementia was detected on neurological examinations. On PiB-PET scans, the patient with PT21 had lower PiB standard uptake values than controls with typical DS or sporadic AD. Plasma Aβ42 was lower than values for demented or non-demented adults with DS. Neuropathological findings showed only a single neuritic plaque and neurofibrillary degeneration consistent with normal aging but not AD. Taken together the findings in this rare patient with PT21 confirm the obligatory role of APP in the clinical, biochemical, and neuropathological findings of AD in DS.
唐氏综合征（DS）患者21号染色体上淀粉样前体蛋白（APP）基因的过表达与脑淀粉样蛋白水平升高及早发性阿尔茨海默病（AD）有关。一名患有表型DS和21号染色体部分三体（PT21）的老年男性，其APP基因未发生三倍体复制，这为研究该基因在痴呆症发病机制中的作用提供了契机。在66至72岁之间进行的多学科研究包括神经心理学测试、独立的神经学检查、使用11C-匹兹堡化合物B（PiB）进行的淀粉样蛋白PET成像、血浆淀粉样β蛋白（Aβ）测量以及脑尸检。临床表型符合DS的典型表现，其智力残疾程度较轻。与患有痴呆症的高功能DS个体相比，他的系列神经心理学测试分数下降不到3%，而患有痴呆症的高功能DS个体分数每年下降17%至28%。神经学检查未发现痴呆。在PiB-PET扫描中，PT21患者的PiB标准摄取值低于典型DS或散发性AD的对照组。血浆Aβ42低于患有DS的痴呆或非痴呆成年人的值。神经病理学发现仅显示一个与正常衰老而非AD一致的神经炎性斑块和神经原纤维变性。综合该罕见PT21患者的研究结果，证实了APP在DS患者AD的临床、生化和神经病理学表现中起必不可少的作用。
