Ozawa Makiko, Chambers James K, Uchida Kazuyuki, Nakayama Hiroyuki
Department of Veterinary Pathology, the University of Tokyo, Tokyo 113-8657, Japan.
J Vet Med Sci. 2016 Jul 1;78(6):997-1006. doi: 10.1292/jvms.15-0624. Epub 2016 Feb 27.
Canine cognitive dysfunction (CCD) is a syndrome that manifests itself in abnormal behaviors, such as disorientation and wandering. β-amyloid deposition in the brain, including the senile plaque (SP) and cerebral amyloid angiopathy (CAA), has been suggested as a major cause of the syndrome. However, the pathological significance of β-amyloid deposition in CCD dogs remains unclear. The present study was conducted using 16 dogs aged 10 years or older to clarify the relationship between the age-related histopathological lesions, such as β-amyloid deposition, in the brain and the clinical symptoms of CCD as evaluated in a questionnaire previously established in a large survey. In addition, age-related brain lesions were assessed in 37 dogs. The pathological lesions were evaluated by the severity of β-amyloid deposition (SP and CAA), the amount of ubiquitin-positive granules (UBQ), GFAP-positive astrocytes, Iba-1-positive microglia and Nissle stain-positive nerve cells. The results revealed that there was no significant correlation between the severities of canine SP and CCD. The SP increased until 14 years old, but decreased thereafter, although the incidence of CCD is high at these ages. The CAA consistently increased with age, but did not correlate greatly with the CCD score. In contrast, the increases of UBQ, astrocytes and microglia were significantly correlated with CCD. Thus, the impairment in the synapse and/or myelin suggested by increased UBQ and glial activation might be involved in CCD pathogenesis, but β-amyloid deposition, especially SP, is not a direct pathogenic factor of CCD.
犬认知功能障碍（CCD）是一种表现为异常行为的综合征，如定向障碍和徘徊。大脑中的β-淀粉样蛋白沉积，包括老年斑（SP）和脑淀粉样血管病（CAA），被认为是该综合征的主要原因。然而，β-淀粉样蛋白沉积在患有CCD的犬中的病理意义仍不清楚。本研究使用了16只10岁及以上的犬，以阐明大脑中与年龄相关的组织病理学病变（如β-淀粉样蛋白沉积）与之前在一项大型调查中建立的问卷所评估的CCD临床症状之间的关系。此外，还对37只犬的与年龄相关的脑部病变进行了评估。通过β-淀粉样蛋白沉积（SP和CAA）的严重程度、泛素阳性颗粒（UBQ）的数量、胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞、离子钙结合衔接分子1（Iba-1）阳性小胶质细胞和尼氏染色阳性神经细胞来评估病理病变。结果显示，犬SP的严重程度与CCD之间没有显著相关性。SP在14岁之前增加，但此后下降，尽管在这些年龄段CCD的发病率很高。CAA随年龄持续增加，但与CCD评分的相关性不大。相比之下，UBQ、星形胶质细胞和小胶质细胞的增加与CCD显著相关。因此，UBQ增加和胶质细胞激活所提示的突触和/或髓鞘损伤可能参与了CCD的发病机制，但β-淀粉样蛋白沉积，尤其是SP，不是CCD的直接致病因素。
