Neuroscience Research, Jesse Brown VA Medical Center, Chicago, IL, USA Department of Pediatrics, University of Illinois Hospital & Health Science System-Children's Hospital, University of Illinois at Chicago, Chicago, IL, USA.
Department of Biopharmaceutical Sciences, Roosevelt University, Schaumburg, IL, USA.
J Alzheimers Dis. 2014;39(1):145-62. doi: 10.3233/JAD-131238.
Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病，约占迟发性非家族性/散发性 AD 的 95%，仅占早发性家族性 AD 的 5%左右。能够提供代表散发性 AD 的相关模型对于测试候选疗法至关重要。新出现的证据表明糖尿病与 AD 之间存在因果关系。患有糖尿病的人患 AD 的可能性增加了 1.5 倍以上。加速衰老的 SAMP8 小鼠模型（SAMP8）显示出 AD 早期发生的许多特征。鉴于糖尿病在 AD 易感性中的作用，以及 SAMP8 非转基因加速衰老小鼠模型的实用性，我们研究了高脂肪饮食诱导的 SAMP8 小鼠实验性 2 型糖尿病是否会引发大脑病理性衰老。结果表明，与非糖尿病 SAMP8 小鼠相比，糖尿病 SAMP8 小鼠表现出大脑淀粉样蛋白-β增加、tau 磷酸化糖原合酶激酶 3β失调、突触小体蛋白免疫反应性降低，并表现出记忆缺陷，表明出现了类似阿尔茨海默病的变化。高脂肪饮食诱导的 2 型糖尿病 SAMP8 小鼠可能代表 AD 的代谢模型。
