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

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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.