Plos one：斑块数量或非早期AD更佳标志物

近日，澳大利亚新南威尔士州立大学医学院神经科学系加尔万医学神经病变研究所发布研究称，阿尔茨海默病（AD）患者斑块数量可能并不是早期AD的最佳标志物，而活化的小胶质细胞可能能够更好地追踪疾病的进展。　
　　近期的阿尔茨海默病（AD）治疗的临床实验均未取得令人满意的成果，这就让人想到其治疗可能需要在疾病早期就开始，而不应等到出现认知方面的症状。这就需要确定AD的早期病理学标志物，淀粉样Aβ斑块可能在其中发挥作用。
　　澳大利亚新南威尔士州立大学医学院神经科学系加尔万医学神经病变研究所通过观察hAPP-J20 AD小鼠模型第6、12、24和36周的病理变化来研究其作用。研究在任何年龄的小鼠中均未发现海马CA3区的神经元缺失，而海马CA1区的神经元丢失在第12周龄时就开始了。随着年龄的增长，神经元缺失的范围更广，并且与活化的小胶质细胞数量有关。胶质化在衰老过程中有一个平台期。在第16和14周龄时，小鼠会出现活动程度增加以及空间记忆力缺损。斑块的出现和Aβ寡聚体的形成是最后的病理变化，在第36周龄才能观察到明显变化，这一点令人惊讶，因为hAPP-J20小鼠是被设计为过度表达Aβ的模型动物。我们的实验提出了一种可能性，即斑块数量可能并不是早期AD的最佳标志物，而活化的小胶质细胞可能能够更好地追踪疾病的进展。
与阿尔茨海默病相关的拓展阅读：

• ACS Chem Neurosci：揭示橄榄油预防阿尔茨海默病机制
• Molecules：草花总黄酮或可用于治疗阿尔茨海默病
• Molecules：草花总黄酮可用于治疗阿尔茨海默病
• JAMA Neurol：睡眠障碍或为阿尔茨海默病早期征象
• AAN2013：阿尔茨海默病药物治疗新靶点
• Transl Psychiatry：阿尔茨海默病新生物标志物—视网膜血管参数 更多信息请点击：有关阿尔茨海默病更多资讯

Neuroinflammation and Neuronal Loss Precede Aβ Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer's Disease.
Abstract
Recent human trials of treatments for Alzheimer’s disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-βAβ? plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression.