Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome.
Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome.
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DOI：
10.1016/j.jalz.2016.08.012
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Granholm AC
中科院分区：
文献类型：
--
作者：
Hamlett ED;Goetzl EJ;Ledreux A;Vasilevko V;Boger HA;LaRosa A;Clark D;Carroll SL;Carmona-Iragui M;Fortea J;Mufson EJ;Sabbagh M;Mohammed AH;Hartley D;Doran E;Lott IT;Granholm AC
患有唐氏综合征（DS）的个体在生命早期表现出阿尔茨海默病（AD）神经病理学和痴呆。AD神经病理学的血液生物标志物将是有价值的，因为DS和AD痴呆的非AD智力残疾在临床上重叠。我们假设，神经元外泌体中淀粉样蛋白-β（Aβ）肽和磷酸化-Tau（P-Tau）的升高可能证明了临床前AD。通过酶联免疫吸附试验定量AD神经致病性蛋白Aβ1-42、P-T181-Tau和P-S396-Tau的神经元外泌体提取物，所述神经元外泌体提取物从患有DS的个体和年龄匹配的对照的血液中纯化。与年龄匹配的对照组相比，早期DS患者的Aβ1-42、P-T181-Tau和P-S396-Tau的神经元外泌体水平显著升高。未观察到显著的性别差异。DS患者中Aβ1-42、P-T181-Tau和P-S396-Tau的这些早期增加可能为靶向治疗的早期干预提供基础。
Individuals with Down syndrome (DS) exhibit Alzheimer’s disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid-beta (Aβ) peptides and phosphorylated-Tau (P-Tau) in neuronal exosomes may document preclinical AD. AD neuropathogenic proteins Aβ1-42, P-T181-Tau and P-S396-Tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls. Neuronal exosome levels of Aβ1-42, P-T181-Tau and P-S396-Tau were significantly elevated in individuals with DS compared to age-matched controls at an early age. No significant gender differences were observed. These early increases in Aβ1-42, P-T181-Tau, and P-S396-Tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.
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