rTg-D: A novel transgenic rat model of cerebral amyloid angiopathy Type-2.
rTg-D: A novel transgenic rat model of cerebral amyloid angiopathy Type-2.
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DOI：
10.1016/j.cccb.2022.100133
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发表时间：
2022
期刊：
影响因子：
--
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中科院分区：
文献类型：
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新型转基因大鼠脑淀粉样血管病模型的建立。家族性突变靶向大脑血管中的淀粉样蛋白积聚。新的大鼠模型产生脑微出血和小血管闭塞。脑淀粉样血管病（Cerebral amyloid angiopathy，CAA）是老年人的常见疾病，是阿尔茨海默病的主要合并症，可引起血管性认知功能障碍和痴呆。以前，我们产生了一个转基因大鼠模型的毛细血管CAA 1型，发展人类疾病的许多病理特征。然而，一个补充的大鼠模型的大血管CAA 2型疾病一直缺乏。建立了一种新的转基因大鼠模型（rTg-D），该模型在脑中产生人类家族性CAA Dutch E22 Q突变体淀粉样β蛋白（Aβ），并形成较大的血管CAA 2型。进行定量生化和病理学分析，以表征CAA的进展和相关的病理学在老龄rTg-D大鼠。rTg-D大鼠开始在脑中积聚Aβ，并在不存在毛细血管CAA-1的情况下，从约18月龄开始出现不同水平的较大血管CAA-2。大血管CAA主要由Aβ40肽组成，在表面软脑膜/软脑膜血管和皮质及丘脑的小动脉中最为突出。脑微出血和小血管闭塞主要存在于受影响的rTg-D大鼠的丘脑区域。与毛细血管CAA-1型相反，rTg-D大鼠较大血管壁内沉积的淀粉样蛋白不促进血管周围星形胶质细胞和小胶质细胞反应，也不积累Aβ伴侣载脂蛋白E。尽管严重程度不同，但rTg-D大鼠特异性地发展较大血管CAA 2型，其反映了人类疾病的许多病理特征，并提供了研究这种疾病发病机制的新模型。
Novel transgenic rats generated to model cerebral amyloid angiopathy. Familial mutation targets amyloid accumulation in larger cerebral vessels. New rat model develops cerebral microbleeds and small vessel occlusions. Cerebral amyloid angiopathy (CAA) is common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a transgenic rat model of capillary CAA type-1 that develops many pathological features of human disease. However, a complementary rat model of larger vessel CAA type-2 disease has been lacking. A novel transgenic rat model (rTg-D) was generated that produces human familial CAA Dutch E22Q mutant amyloid β-protein (Aβ) in brain and develops larger vessel CAA type-2. Quantitative biochemical and pathological analyses were performed to characterize the progression of CAA and associated pathologies in aging rTg-D rats. rTg-D rats begin to accumulate Aβ in brain and develop varying levels of larger vessel CAA type-2, in the absence of capillary CAA type-1, starting around 18 months of age. Larger vessel CAA was mainly composed of the Aβ40 peptide and most prominent in surface leptomeningeal/pial vessels and arterioles of the cortex and thalamus. Cerebral microbleeds and small vessel occlusions were present mostly in the thalamic region of affected rTg-D rats. In contrast to capillary CAA type-1 the amyloid deposited within the walls of larger vessels of rTg-D rats did not promote perivascular astrocyte and microglial responses or accumulate the Aβ chaperone apolipoprotein E. Although variable in severity, the rTg-D rats specifically develop larger vessel CAA type-2 that reflects many of the pathological features of human disease and provide a new model to investigate the pathogenesis of this condition.
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影响因子：
2.9
作者：
Garai, Kanchan;Verghese, Philip B.;Baban, Berevan;Holtzman, David M.;Frieden, Carl
通讯作者：
Frieden, Carl
DOI：
10.1016/s0169-328x(02)00647-2
发表时间：
2003-01-31
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Burns, MP;Noble, WJ;Duff', K
通讯作者：
Duff', K
影响因子：
6.3
作者：
Lee, Hedok;Xu, Feng;Benveniste, Helene
通讯作者：
Benveniste, Helene
影响因子：
82.9
作者：
Deane, R;Yan, SD;Zlokovic, B
通讯作者：
Zlokovic, B
影响因子：
4.8
作者：
Davis, J;Xu, F;Van Nostrand, WE
通讯作者：
Van Nostrand, WE