Comparative evolutionary studies on the expmssion of dementia-related genes in aging nonhuman animals

我们研究了β-淀粉样蛋白（A β）和β-淀粉样蛋白前体蛋白（APP）在狗的神经元和非神经元组织中的免疫组织化学定位。A β仅在老年犬大脑的老年斑中检出。APP在神经元胞体和纤维中的表达与年龄无关。此外，腺上皮细胞的APP的免疫阳性。因此，这表明，APP可能是在非神经元上皮组织在dogs.Gene表达的狗脑进行了研究，使用阵列膜过滤器制备的人类分析。脑老化相关基因在老年犬的脑中上调。然而，APP基因的表达在老年人的大脑中并没有增加。通过分形维数（FD）方法对所得结构进行了形态学评价。低FD的SP似乎比高FD的SP更小，密度更低。计算机模拟的低FD SP可能对应于体内猫SP，计算机模拟的高FD SP可能对应于其他动物物种的SP。根据本研究结果，猫脑中SP的形成可能不同于其他动物，提示猫脑中有一种特殊的A β沉积过程，APP可能在脑和某些腺体组织中起重要作用，并可能在狗脑中因衰老而异常降解为A β。而APP的表达在整个生命过程中是稳定的。APP的这种异常降解和A β分析的抑制可能对犬脑中的A β沉积至关重要。

We examined the immunohistochemical localization of beta-amyloid (A beta) and beta-amyloid precursor protein (APP) in the neuronal and non-neuronal tissues of dogs. A beta was detected only in the senile plaque (SP) in cerebrum of aged dogs. APP was expressed in the neuronal cell body and fiber independent of the age. In addition, glandular epithelial cells were immunopositive for APP. Thus, it is suggested that APP may be expressed in the non-neuronal epithelial tissues in dogs.Gene expressions of the canine brain was investigated using array membrane filters prepared for human analysis. Brain aging-related genes were upregulated in the brain from aged dogs. However, the expression of the APP gene was not increased in the aged brains.An attempt to create SPs of various shapes in silica was performed, using computer software programs. The resultant structures were morphologically evaluated by the fractal dimension (FD) method. SPs with low FD seemed to be smaller in size and less dense than those with higher FD. The low-FD SPs in silico may correspond to feline SPs in vivo, and the high-FD SP in silico to SPs of other animal species. According to the present results, SP formation in the aged feline brain may be different from that of other animal species, indicating a special A beta deposition process in cats.APP may play an important function(s) in the brain and some glandular tissues, and may be abnormally degraded to A beat in the brain by aging in dogs. However, the expression of APP was stable during life. Such abnormal degradation of APP and the inhibition of A betalysis may be crucial for A beta deposition in the canine brain.