Yoo B C, Cairns N, Fountoulakis M, Lubec G
Department of Pediatrics, University of Vienna, Austria.
Dement Geriatr Cogn Disord. 2001 May-Jun;12(3):219-25. doi: 10.1159/000051261.
Although it is well-known that synaptosomal proteins are deranged in neurodegenerative disorders, no information is available at the protein-chemical level as mainly immunochemical or immunohistochemical data were reported previously. We therefore investigated synaptosomal proteins in brain specimens from patients with Down syndrome (DS) and Alzheimer's disease (AD) to challenge the DS synaptic pathology as well as the relevance of DS to AD in synaptic pathology. For the aim of this study, we employed two-dimensional electrophoresis and matrix-associated laser desorption ionization mass spectroscopy and determined beta-soluble N-ethylmaleimide-sensitive factor attachment protein (beta-SNAP), gamma-SNAP and synaptotagmin I (SYT I) in 7 individual brain regions of controls and patients with DS and AD. In DS brain, beta-SNAP was significantly reduced in temporal cortex (p < 0.01). SYT I (p65) and SYT I (pI 7.0) were significantly reduced in thalamus (p < 0.01 and p < 0.05, respectively). In AD brain, beta-SNAP was significantly decreased in temporal cortex (p < 0.05). SYT I (p65) was significantly reduced in cerebellum (p < 0.05), and temporal (p < 0.001) and parietal cortex (p < 0.01). SYT I (pI 7.0) was significantly reduced in temporal (p < 0.001) and parietal cortex (p < 0.01) and thalamus (p < 0.01). gamma-SNAP did not show any change in both DS and AD. The findings may explain impaired synaptogenesis in DS and AD brain, which is well documented in DS brain already early in life, and/or synaptosomal loss secondary to neuronal loss observed in both neurodegenerative disorders. It may also represent, reflect or account for the impaired neuronal transmission in DS and AD, caused by deterioration of the exocytic machinery. Here, we provide evidence for several deranged synaptosomal proteins in several brain regions at the protein level indicating deficient synaptosomal wiring of the brain in DS and AD.
尽管众所周知，突触体蛋白在神经退行性疾病中会发生紊乱，但在蛋白质化学水平上尚无相关信息，因为此前主要报道的是免疫化学或免疫组织化学数据。因此，我们研究了唐氏综合征（DS）和阿尔茨海默病（AD）患者脑标本中的突触体蛋白，以探讨DS突触病理学以及DS与AD在突触病理学中的相关性。为了本研究的目的，我们采用二维电泳和基质辅助激光解吸电离质谱法，测定了对照组、DS患者和AD患者7个不同脑区中的β-可溶性N-乙基马来酰亚胺敏感因子附着蛋白（β-SNAP）、γ-SNAP和突触结合蛋白I（SYT I）。在DS脑中，颞叶皮质中的β-SNAP显著降低（p < 0.01）。丘脑（分别为p < 0.01和p < 0.05）中的SYT I（p65）和SYT I（pI 7.0）显著降低。在AD脑中，颞叶皮质中的β-SNAP显著降低（p < 0.05）。小脑（p < 0.05）、颞叶（p < 0.001）和顶叶皮质（p < 0.01）中的SYT I（p65）显著降低。颞叶（p < 0.001）、顶叶皮质（p < 0.01）和丘脑（p < 0.01）中的SYT I（pI 7.0）显著降低。γ-SNAP在DS和AD中均未显示任何变化。这些发现可能解释了DS和AD脑中突触发生受损的情况，这在DS脑中早在生命早期就有充分记录，和/或解释了在这两种神经退行性疾病中观察到的继发于神经元丢失的突触体丢失。它也可能代表、反映或解释了由胞吐机制恶化导致的DS和AD中神经元传递受损的情况。在此，我们在蛋白质水平上为几个脑区中几种紊乱的突触体蛋白提供了证据，表明DS和AD脑中突触体连接存在缺陷。
