The Social Lab, Department of Psychology and Neuroscience, Dalhousie University, Halifax, B3H 4R2, Canada.
The Social Lab, Department of Psychology and Neuroscience, Dalhousie University, Halifax, B3H 4R2, Canada.
Neurosci Biobehav Rev. 2020 May;112:634-647. doi: 10.1016/j.neubiorev.2020.02.012. Epub 2020 Feb 15.
Transgenic mouse models have been used extensively to model the cognitive impairments arising from Alzheimer's disease (AD)-related pathology. However, less is known about the relationship between AD-related pathology and the behavioural and psychological symptoms of dementia (BPSD) commonly presented by patients. This review discusses the BPSD-like behaviours recapitulated by several mouse models of AD-related pathology, including the APP/PS1, Tg2576, 3xTg-AD, 5xFAD, and APP23 models. Current evidence suggests that social withdrawal and depressive-like behaviours increase with progressive neuropathology, and increased aggression and sleep-wake disturbances are present even at early stages; however, there is no clear evidence to support increased anxiety-like behaviours, agitation (hyperactivity), or general apathy. Overall, transgenic mouse models of AD-related pathology recapitulate some of the BPSD-like behaviours associated with AD, but these behaviours vary by model. This reflects the patient population, where AD patients typically exhibit one or more BPSD, but rarely all symptoms at once. As a result, we suggest that transgenic mouse models are an important tool to investigate the pathology underlying BPSD in human AD patients.
转基因小鼠模型已被广泛用于模拟与阿尔茨海默病(AD)相关病理学引起的认知障碍。然而,对于 AD 相关病理学与患者常见的痴呆症的行为和心理症状(BPSD)之间的关系知之甚少。本综述讨论了几种 AD 相关病理学的小鼠模型再现的 BPSD 样行为,包括 APP/PS1、Tg2576、3xTg-AD、5xFAD 和 APP23 模型。目前的证据表明,随着神经病理学的进展,社交回避和抑郁样行为会增加,甚至在早期就会出现攻击性增强和睡眠-觉醒障碍;然而,没有明确的证据支持焦虑样行为、烦躁(多动)或普遍冷漠增加。总体而言,AD 相关病理学的转基因小鼠模型再现了一些与 AD 相关的 BPSD 样行为,但这些行为因模型而异。这反映了患者群体,AD 患者通常表现出一种或多种 BPSD,但很少同时出现所有症状。因此,我们认为转基因小鼠模型是研究人类 AD 患者 BPSD 病理基础的重要工具。