Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo, Japan.
J Vet Med Sci. 2022 Nov 18;84(12):1563-1573. doi: 10.1292/jvms.22-0386. Epub 2022 Oct 25.
Cerebral amyloid β (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). There are several molecular species of Aβ, including Aβ40, Aβ42, and Aβ43, and the pathological roles of Aβ43 have attracted particular attention in recent years. Aβ43 is mainly deposited as senile plaques (SPs) in AD brains, and is known to be more amyloidogenic and neurotoxic than Aβ42 and Aβ40. Aβ40 and Aβ42 deposition have been demonstrated in several animal species, while Aβ43 deposition has not been studied in animals. The brains of sea lions, dogs, and cats exhibit unique age-related Aβ pathologies. In the present study, the deposition patterns of Aβ40, Aβ42, and Aβ43 were examined immunohistochemically in the brains of aged dogs (n=52), sea lions (n=5), and cats (n=17). In dogs, most cerebral amyloid angiopathy (CAA) lesions and primitive SPs were positive for Aβ42, Aβ43, and Aβ40. However, diffuse SPs and capillary CAA lesions were negative for Aβ40. In sea lions, all SPs and most CAA lesions were positive for Aβ42, Aβ43, and Aβ40, while capillary CAA lesions were negative for Aβ40. In cats, Aβ42-immunopositive granular aggregates and arteriole and capillary CAA lesions were positive for Aβ43, but negative for Aβ40. Double-labelling immunohistochemistry revealed the co-localization of Aβ42 and Aβ43. These findings suggest that Aβ43 and Aβ42 are frequently deposited in the brains of Carnivora animals and may play an important role in Aβ pathology.
脑淀粉样蛋白 β（Aβ）沉积是阿尔茨海默病（AD）的病理标志之一。Aβ 有几种分子亚型，包括 Aβ40、Aβ42 和 Aβ43，近年来 Aβ43 的病理作用引起了特别关注。Aβ43 主要在 AD 大脑中沉积为老年斑（SPs），已知其比 Aβ42 和 Aβ40 更具淀粉样变性和神经毒性。Aβ40 和 Aβ42 的沉积已在几种动物物种中得到证实，而 Aβ43 的沉积尚未在动物中进行研究。海狮、狗和猫的大脑表现出独特的与年龄相关的 Aβ 病理学。在本研究中，通过免疫组织化学方法检查了老年狗（n=52）、海狮（n=5）和猫（n=17）大脑中 Aβ40、Aβ42 和 Aβ43 的沉积模式。在狗中，大多数脑淀粉样血管病（CAA）病变和原始 SPs 对 Aβ42、Aβ43 和 Aβ40 呈阳性。然而，弥漫性 SPs 和毛细血管 CAA 病变对 Aβ40 呈阴性。在海狮中，所有 SPs 和大多数 CAA 病变对 Aβ42、Aβ43 和 Aβ40 呈阳性，而毛细血管 CAA 病变对 Aβ40 呈阴性。在猫中，Aβ42 免疫阳性颗粒聚集物和小动脉和毛细血管 CAA 病变对 Aβ43 呈阳性，但对 Aβ40 呈阴性。双重标记免疫组织化学显示 Aβ42 和 Aβ43 的共定位。这些发现表明 Aβ43 和 Aβ42 经常在食肉动物的大脑中沉积，并可能在 Aβ 病理学中发挥重要作用。
