Institute of Neuroscience, Technical University of Munich, 80802 Munich, Germany; Munich Cluster for Systems Neurology, Technical University of Munich, 80802 Munich, Germany; Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany.
Institute of Neuroscience, Technical University of Munich, 80802 Munich, Germany; Munich Cluster for Systems Neurology, Technical University of Munich, 80802 Munich, Germany.
Semin Cell Dev Biol. 2023 Apr;139:24-34. doi: 10.1016/j.semcdb.2022.03.013. Epub 2022 Mar 22.
One of the hallmarks of Alzheimer's disease (AD) is structural cell damage and neuronal death in the brains of affected individuals. As these changes are irreversible, it is important to understand their origins and precursors in order to develop treatment strategies against AD. Here, we review evidence for AD-specific impairments of glutamatergic synaptic transmission by relating evidence from human AD subjects to functional studies in animal models of AD. The emerging picture is that early in the disease, the accumulation of toxic β-amyloid aggregates, particularly dimers and low molecular weight oligomers, disrupts glutamate reuptake, which leads to its extracellular accumulation causing neuronal depolarization. This drives the hyperactivation of neurons and might facilitate neuronal damage and degeneration through glutamate neurotoxicity.
阿尔茨海默病（AD）的特征之一是受影响个体大脑中的结构细胞损伤和神经元死亡。由于这些变化是不可逆转的，因此了解其起源和前兆对于开发针对 AD 的治疗策略非常重要。在这里，我们通过将人类 AD 患者的证据与 AD 动物模型的功能研究相关联，来回顾 AD 特异性谷氨酸能突触传递损伤的证据。新兴的图景是，在疾病早期，有毒的β-淀粉样蛋白聚集体（尤其是二聚体和低分子量寡聚体）的积累会破坏谷氨酸的再摄取，导致其在细胞外积累，从而导致神经元去极化。这会驱动神经元的过度激活，并可能通过谷氨酸神经毒性促进神经元损伤和退化。
