Goetzl Edward J, Kapogiannis Dimitrios, Schwartz Janice B, Lobach Iryna V, Goetzl Laura, Abner Erin L, Jicha Gregory A, Karydas Anna M, Boxer Adam, Miller Bruce L
Department of Medicine, University of California, San Francisco, San Francisco, California, USA;
Jewish Home of San Francisco, San Francisco, California, USA.
FASEB J. 2016 Dec;30(12):4141-4148. doi: 10.1096/fj.201600816R. Epub 2016 Sep 6.
Synaptic dysfunction occurs early in senile dementias, presumably as a result of decreased levels of functional synaptic proteins as found in autopsied brains of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD). Plasma neuronal-derived exosomes (NDEs) were recovered by precipitation and immunoabsorption from 12 patients with AD, 16 with FTD, and 28 controls in a cross-sectional study, and from 9 patients with AD, 10 with FTD, and 19 controls in a longitudinal study. Six synaptic proteins in NDE extracts were quantified by ELISAs and normalized for exosome amounts. NDE levels of synaptophysin, synaptopodin, synaptotagmin-2, and neurogranin were significantly lower in patients with FTD and AD than in controls, but those of growth-associated protein 43 and synapsin 1 were reduced only in patients with AD. Functionally relevant phosphorylation of synapsin 1 serine 9 was reduced in patients with FTD and AD, although total synapsin 1 protein was higher in FTD than in controls. NDE levels of synaptotagmin, synaptophysin, and neurogranin were decreased years before dementia in patients with FTD and AD. NDE levels of synaptopodin, synaptotagmin, and synaptophysin, but not of amyloid β-peptide 42 or P-T181-tau, were correlated significantly with cognition assessed by mini-mental state examination or AD assessment scale-cognitive subscale. NDE synaptic proteins may be useful preclinical indices and progression measures in senile dementias.-Goetzl, E. J., Kapogiannis, D., Schwartz, J. B., Lobach, I. V., Goetzl, L., Abner, E. L., Jicha, G. A., Karydas, A. M., Boxer, A., Miller, B. L. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease.
突触功能障碍在老年痴呆症早期就会出现，可能是由于功能性突触蛋白水平降低，这在阿尔茨海默病（AD）或额颞叶痴呆（FTD）患者的尸检大脑中已被发现。在一项横断面研究中，通过沉淀和免疫吸附从12例AD患者、16例FTD患者和28例对照者中回收血浆神经元衍生外泌体（NDEs）；在一项纵向研究中，从9例AD患者、10例FTD患者和19例对照者中回收。通过酶联免疫吸附测定法对NDE提取物中的六种突触蛋白进行定量，并根据外泌体数量进行标准化。FTD和AD患者的NDE中突触素、突触足蛋白、突触结合蛋白-2和神经颗粒素的水平显著低于对照组，但生长相关蛋白43和突触素1仅在AD患者中降低。尽管FTD患者的总突触素1蛋白高于对照组，但FTD和AD患者中突触素1丝氨酸9的功能相关磷酸化降低。FTD和AD患者在出现痴呆症状前数年，NDE中突触结合蛋白、突触素和神经颗粒素的水平就已下降。NDE中突触足蛋白、突触结合蛋白和突触素的水平与通过简易精神状态检查或AD评估量表认知子量表评估的认知显著相关，但淀粉样β肽42或P-T181- tau的水平则不然。NDE突触蛋白可能是老年痴呆症有用的临床前指标和病情进展测量指标。——戈茨尔，E. J.，卡波吉安尼斯，D.，施瓦茨，J. B.，洛巴赫，I. V.，戈茨尔，L.，阿伯纳，E. L.，吉查，G. A.，卡里达斯，A. M.，博克瑟，A.，米勒，B. L. 额颞叶痴呆和阿尔茨海默病神经元外泌体中突触蛋白减少
