Cassel Jean-Christophe, Mathis Chantal, Majchrzak Monique, Moreau Pierre-Henri, Dalrymple-Alford John C
LINC UMR 7191, Université Louis Pasteur, CNRS, Institut Fédératif de Recherche IFR 37, GDR CNRS 2905, Strasbourg, France.
Neurodegener Dis. 2008;5(5):304-17. doi: 10.1159/000135615. Epub 2008 Jun 3.
One century after Alzheimer's initial report, a variety of animal models of Alzheimer's disease (AD) are being used to mimic one or more pathological signs viewed as critical for the evolution of cognitive decline in dementia. Among the most common are, (a) traditional lesion models aimed at reproducing the degeneration of one of two key brain regions affected in AD, namely the cholinergic basal forebrain (CBF) and the transentorhinal region, and (b) transgenic mouse models aimed at reproducing AD histopathological hallmarks, namely amyloid plaques and neurofibrillary tangles. These models have provided valuable insights into the development and consequences of the pathology, but they have not consistently reproduced the severity of memory deficits exhibited in AD. The reasons for this lack of correspondence with the severity of expected deficits may include the limited replication of multiple neuropathology in potentially key brain regions. A recent lesion model in the rat found that severe memory impairment was obtained only when the two traditional lesions were combined together (i.e. conjoint CBF and entorhinal cortex lesions), indicative of a dramatic impact on cognitive function when there is coexisting, rather than isolated, damage in these two brain regions. It is proposed that combining AD transgenic mouse models with additional experimental damage to both the CBF and entorhinal regions might provide a unique opportunity to further understand the evolution of the disease and improve treatments of severe cognitive dysfunction in neurodegenerative dementias.
在阿尔茨海默病首次报告后的一个世纪里，多种阿尔茨海默病（AD）动物模型被用于模拟一种或多种被视为对痴呆症认知衰退演变至关重要的病理体征。其中最常见的有：（a）传统损伤模型，旨在重现AD中受影响的两个关键脑区之一的退化，即胆碱能基底前脑（CBF）和内嗅区；（b）转基因小鼠模型，旨在重现AD的组织病理学特征，即淀粉样斑块和神经原纤维缠结。这些模型为病理的发展和后果提供了有价值的见解，但它们并未始终如一地重现AD中出现的记忆缺陷的严重程度。与预期缺陷严重程度缺乏对应关系的原因可能包括潜在关键脑区中多种神经病理学的复制有限。最近在大鼠身上的一个损伤模型发现，只有当两种传统损伤结合在一起时（即联合CBF和内嗅皮质损伤），才会出现严重的记忆障碍，这表明当这两个脑区同时存在损伤而非孤立损伤时，对认知功能有巨大影响。有人提出，将AD转基因小鼠模型与对CBF和内嗅区的额外实验性损伤相结合，可能会为进一步了解疾病的演变以及改善神经退行性痴呆中严重认知功能障碍的治疗提供独特的机会。
