Culling Less Fit Neurons Protects against Amyloid-β-Induced Brain Damage and Cognitive and Motor Decline
Culling Less Fit Neurons Protects against Amyloid-β-Induced Brain Damage and Cognitive and Motor Decline
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DOI：
10.1016/j.celrep.2018.11.098
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发表时间：
2018-12-26
期刊：
影响因子：
8.8
通讯作者：
Moreno, Eduardo
中科院分区：
文献类型：
--
作者：
Coelho, Dina S.;Schwartz, Silvia;Moreno, Eduardo
阿尔茨海默病（AD）是痴呆症的最常见形式，损害认知和运动功能。AD的病理学标志之一是神经元损失，这在AD的小鼠模型中没有反映。因此，神经元死亡的作用仍然不确定。在这里，我们使用了一个果蝇AD模型，表达了一种分泌形式的人淀粉样蛋白β 42肽，并表明它概括了AD病理学的关键方面，包括神经元死亡和长期记忆受损。我们发现，神经元凋亡是由细胞适应度驱动的神经元剔除介导的，它选择性地将受损的神经元从脑回路中清除。我们证明，去除不太适合的神经元延迟β-淀粉样蛋白诱导的脑损伤，并防止认知和运动能力下降，这表明与常识相反，神经元死亡可能对AD有有益的影响。
Alzheimer's disease (AD) is the most common form of dementia, impairing cognitive and motor functions. One of the pathological hallmarks of AD is neuronal loss, which is not reflected in mouse models of AD. Therefore, the role of neuronal death is still uncertain. Here, we used a Drosophila AD model expressing a secreted form of human amyloid- beta 42 peptide and showed that it recapitulates key aspects of AD pathology, including neuronal death and impaired long-term memory. We found that neuronal apoptosis is mediated by cell fitnessdriven neuronal culling, which selectively eliminates impaired neurons from brain circuits. We demonstrated that removal of less fit neurons delays beta-amyloid- induced brain damage and protects against cognitive and motor decline, suggesting that contrary to common knowledge, neuronal death may have a beneficial effect in AD.