Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70228, Cuidad Universitaria, CDMX, CP 04510, Mexico.
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70228, Cuidad Universitaria, CDMX, CP 04510, Mexico.
J Neuroimmunol. 2023 Sep 15;382:578150. doi: 10.1016/j.jneuroim.2023.578150. Epub 2023 Jul 13.
Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aβ in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies. In the present study, we documented interesting new features in the thalamus of Tg-SwDI mice: 1) a sharp increase in the expression of ionized calcium-binding adapter molecule 1 (Iba-1) in microglia in 6-month-old animals; 2) microglia clustering at six months that disappeared in old animals; 3) N-truncated/modified AβN3(pE) peptide in 9-month-old female and 12-month-old male mice; 4) an age-dependent increase in translocator protein (TSPO) expression. These findings reinforce the versatility of this model for studying multiple pathological issues involved in AD and CAA.
流行病学研究表明，阿尔茨海默病（AD）和脑淀粉样血管病（CAA）经常同时发生；然而，其确切机制尚不清楚。已经开发出一种独特的动物模型（Tg-SwDI 小鼠）来研究脑实质和血管 Aβ的早期、强烈积累。Tg-SwDI 小鼠已被广泛用于研究 AD/CAA 患者中观察到的脑血管功能障碍、神经炎症、神经退行性变和认知能力下降的机制，并设计生物标志物和治疗策略。在本研究中，我们记录了 Tg-SwDI 小鼠丘脑的一些有趣的新特征：1）6 月龄动物小胶质细胞中离子钙结合接头分子 1（Iba-1）的表达急剧增加；2）6 月龄时的小胶质细胞聚集，在老年动物中消失；3）9 月龄雌性和 12 月龄雄性小鼠中的 N 截断/修饰 AβN3(pE)肽；4）TSPO 表达随年龄的依赖性增加。这些发现增强了该模型用于研究 AD 和 CAA 涉及的多种病理问题的多功能性。
