Spines, plasticity, and cognition in Alzheimer's model mice.
Spines, plasticity, and cognition in Alzheimer's model mice.
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DOI：
10.1155/2012/319836
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发表时间：
2012
影响因子：
3.1
通讯作者：
Knafo S
中科院分区：
文献类型：
--
作者：
Spires-Jones T;Knafo S
阿尔茨海默病(AD)的病理特征--广泛的突触和神经元丢失，老年斑中淀粉样β蛋白(Aβ)的病理性积聚，以及神经纤维缠结中tau的过度磷酸化--已经知道了几十年，但AD病理与痴呆之间的联系和有效的治疗策略仍然不清楚。转基因小鼠是基于罕见的家族性阿尔茨海默病和额颞叶痴呆而开发的，使研究人员能够详细测试AD相关病理的结构、功能和行为后果。在这里，我们回顾了转基因AD模型的工作，该模型研究了树突棘结构、突触功能和认知的退化。综上所述，这些数据支持AD发病机制的模型，在该模型中，可溶性Aβ启动突触功能障碍和丢失，以及tau的病理变化，这有助于突触和神经元的丢失。这些突触结构和功能的改变以及突触和神经元的丢失导致神经系统功能障碍，从而导致认知障碍。了解阿尔茨海默病中痴呆的基础将是开发和评估这种广泛和破坏性疾病的治疗方法的关键。
The pathological hallmarks of Alzheimer's disease (AD)—widespread synaptic and neuronal loss and the pathological accumulation of amyloid-beta peptide (Aβ) in senile plaques, as well as hyperphosphorylated tau in neurofibrillary tangles—have been known for many decades, but the links between AD pathology and dementia and effective therapeutic strategies remain elusive. Transgenic mice have been developed based on rare familial forms of AD and frontotemporal dementia, allowing investigators to test in detail the structural, functional, and behavioral consequences of AD-associated pathology. Here, we review work on transgenic AD models that investigate the degeneration of dendritic spine structure, synaptic function, and cognition. Together, these data support a model of AD pathogenesis in which soluble Aβ initiates synaptic dysfunction and loss, as well as pathological changes in tau, which contribute to both synaptic and neuronal loss. These changes in synapse structure and function as well as frank synapse and neuronal loss contribute to the neural system dysfunction which causes cognitive deficits. Understanding the underpinnings of dementia in AD will be essential to develop and evaluate therapeutic approaches for this widespread and devastating disease.
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DOI：
10.1073/pnas.1012851108
发表时间：
2010-12-28
影响因子：
11.1
作者：
Caccamo, Antonella;Maldonado, Monica A.;Oddo, Salvatore
通讯作者：
Oddo, Salvatore
影响因子：
64.8
作者：
Chen, GQ;Chen, KS;Morris, RGM
通讯作者：
Morris, RGM
影响因子：
5.3
作者：
Comery, TA;Martone, RL;Marquis, KL
通讯作者：
Marquis, KL
影响因子：
4.2
作者：
Cotel, Marie-Caroline;Jawhar, Sadim;Wirths, Oliver
通讯作者：
Wirths, Oliver
影响因子：
82.9
作者：
Backskai, BJ;Kajdasz, ST;Hyman, BT
通讯作者：
Hyman, BT