Preserved neurogenesis in non-demented individuals with AD neuropathology.
Preserved neurogenesis in non-demented individuals with AD neuropathology.
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DOI：
10.1038/srep27812
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发表时间：
2016-06-14
影响因子：
4.6
通讯作者：
Micci MA
中科院分区：
文献类型：
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作者：
Briley D;Ghirardi V;Woltjer R;Renck A;Zolochevska O;Taglialatela G;Micci MA
尽管存在通常与完全症状性阿尔茨海默病（AD）相关的神经病理学，但很少有个体保持认知完整，我们将其称为非痴呆性阿尔茨海默病神经病理学（NDAN）。了解其认知抵抗的相关机制可能会揭示治疗AD相关痴呆的新策略。为了实现这一目标，我们确定了海马神经干细胞（NSCs）的数量，并研究了NDAN和AD受试者中几种miRNA的表达。本研究采用激光捕获显微切割技术，结合免疫荧光技术，对尸检人海马DG进行qRT-PCR miRNA分析。与AD受试者相比，NDAN个体DG中SOX 2 + NSC的数量显著增加。此外，发现SOX 2 + NSC的患病率与认知能力相关。与AD患者相比，NDAN患者中调节神经发生的miRNA减少。NDAN个体中增加的NSC和新神经元数量与调节miRNA的独特表达相关，并强烈支持神经发生在部分介导这些个体抵抗AD病理负担的能力中的作用。
Rare individuals remain cognitively intact despite the presence of neuropathology usually associated with fully symptomatic Alzheimer’s disease (AD), which we refer to as Non-Demented with Alzheimer’s disease Neuropathology (NDAN). Understanding the involved mechanism(s) of their cognitive resistance may reveal novel strategies to treat AD-related dementia. In the pursuit of this goal, we determined the number of hippocampal neural stem cells (NSCs) and investigated the expression of several miRNAs in NDAN and AD subjects. Laser-capture microdissection of autopsy human hippocampus DG and qRT-PCR miRNA analyses were combined with immunofluorescence in this study. The number of SOX2+ NSCs in the DG was significantly increased in NDAN individuals as compared to AD subjects. Further, the prevalence of SOX2+ NSCs was found to correlate with cognitive capacity. Neurogenesis-regulating miRNAs were decreased in NDAN individuals as compared to AD patients. An increased number of NSCs and new neurons in NDAN individuals is associated with a unique expression of regulating miRNAs and strongly support a role of neurogenesis in mediating, in part, the ability of these individuals to resist the pathological burden of AD.