阿茲海默症是一種神經退化性疾病,而患者腦部堆積類澱粉斑塊和神經纖維纏結是其主要的病理特徵。Klotho 蛋白的表現量被發現能夠影響動物的壽命,且相關基因的突變缺失會縮短小鼠的壽命,並具有加速老化的特色。本研究以不同KL基因表現量的小鼠為實驗對象,觀察週齡和基因表現量是否會影響其嗅球與海馬迴的組織型態及類澱粉斑塊堆積情形。在體重及臟器重量統計結果中,研究發現六週齡和八週齡Kl-/-小鼠之體重及各臟器重量均顯著低於相應週齡之Kl+/+及Kl+/-小鼠。在嗅球的蘇木紫-伊紅染色結果中,研究發現六週齡和八週齡Kl-/-小鼠具有大量僧帽細胞死亡的現象。在海馬迴的蘇木紫-伊紅染色結果中,結果顯示六週齡和八週齡Kl-/-母鼠的CA1有大量錐狀細胞死亡。在海馬迴的剛果紅染色及免疫組織化學染色結果中,研究則發現六週齡和八週齡之Kl+/-及Kl-/-小鼠均有類澱粉斑塊的堆積情形,且該表現於八週齡組更加明顯。這些結果表明六週齡和八週齡KL基因表現缺失小鼠的嗅覺功能可能有所損傷,且其海馬迴具有類澱粉斑塊沉積情形,而該現象也暗示KL基因表現缺失小鼠可能適合應用於老化相關的阿茲海默症研究。
Alzheimer''s disease is a neurodegenerative disease, and the accumulation of amyloid plaques and neurofibrillary tangles in the brain is the main pathological feature. The expression of Klotho protein was found to influence the animal lifespan, and the related gene mutation can shorten the lifespan of mice and accompany with accelerated aging progression. In this study, we used mice that have different kl gene phenotypes as our experimental animals, and observed whether the age and gene expression could affect the tissue morphology and amyloid accumulation of the olfactory bulbs and hippocampus. The statistics results of body weights and organ weights show that the body weights and several organ weights of six and eight week Kl-/- mice were significantly lower than Kl+/+ and Kl+/- mice at the corresponding age. In the results of the hematoxylin-eosin staining of the olfactory bulbs, we found that six and eight week Kl-/- mice had a large amount of mitral cells death appearance. In the results of the hematoxylin-eosin staining of the hippocampus, we found that six and eight week Kl-/- female mice had a large amount of pyramidal cells death appearance. Additionally, Congo red stain and immunohistochemistry stain of hippocampus showed that six and eight week Kl+/- and Kl-/- mice had amyloid plaques accumulation. Moreover, the eight-week group has pronounced expression in comparison with six-week group. These results indicate that the olfactory functions of six- and eight-week Klotho-deficient mice probably may be impaired, and their hippocampus have amyloid plaques deposition, suggesting that Klotho-deficient mice could be applied in studying the aging-related Alzheimer''s disease.