Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
Eur J Neurol. 2011 Mar;18(3):410-24. doi: 10.1111/j.1468-1331.2010.03166.x.
Alzheimer's disease and Schizophrenia are two common diseases of the brain with significant differences in neuropathology, etiology and symptoms. This dissimilarity in the two diseases makes a comparison of the two ideal for detecting molecular substrates that are common to brain disorders in general.
In this study, we compared gene expression profiles across multiple brain areas, taken postmortem from patients with well-characterized Alzheimer's disease and Schizophrenia, and from cognitively normal control group with no neuro- or psychopathology.
Although the totality of gene expression changes in the two diseases is dissimilar, a subset of genes appears to play a role in both diseases in specific brain regions. We find at Brodmann area 22, the superior temporal gyrus, a statistically significant number of genes with apparently disregulated expression in both diseases. Furthermore, we found genes that differentiate the two diseases from the control across multiple brain regions, and note that these genes were usually down-regulated. Brodmann area 8, part of the superior frontal cortex, is relatively abundant with them.
We show overwhelming statistical evidence for Alzheimer's and Schizophrenia sharing a specific molecular background at the superior temporal gyrus. We suggest that impairment of the regulation of autophagy pathway is shared, in BA 22, by the two diseases.
阿尔茨海默病和精神分裂症是两种常见的脑部疾病,在神经病理学、病因和症状上有显著差异。这两种疾病的差异使得将它们进行比较成为检测一般脑部疾病共同的分子基础的理想方法。
在这项研究中,我们比较了来自具有明确特征的阿尔茨海默病和精神分裂症患者以及认知正常、无神经或精神病理学的对照组的多个脑区死后的基因表达谱。
尽管两种疾病的总基因表达变化不同,但在特定脑区,似乎有一组基因在两种疾病中都发挥作用。我们发现,在布罗德曼区 22(颞上回),有相当数量的基因在两种疾病中表达明显失调。此外,我们发现了可以区分两种疾病与对照组的基因,并且注意到这些基因通常下调。它们在额上回的布罗德曼区 8 中相对丰富。
我们展示了压倒性的统计证据,表明阿尔茨海默病和精神分裂症在颞上回具有共同的特定分子背景。我们认为,自噬途径的调节受损在 BA 22 中是两种疾病共有的。