Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
J Alzheimers Dis. 2010;22(3):699-714. doi: 10.3233/JAD-2010-101089.
Alzheimer's disease (AD) is caused by the accumulation of amyloid-β (Aβ), which induces progressive decline in learning, memory, and other cognitive functions. Aβ is a neurotoxic protein that disrupts calcium signaling in neurons and alters synaptic plasticity. These effects lead to loss of synapses, neural network dysfunction, and inactivation of neuronal signaling. However, the precise mechanism by which Aβ causes neurodegeneration is still not clear, despite decades of intensive research. The role of astrocytes in early cognitive decline is a major component of disease pathology that has been poorly understood. Recent research suggests that astrocytes are not simply passive support cells for neurons, but are active participants in neural information processing in the brain. Aβ can disrupt astrocytic calcium signaling and gliotransmitter release, processes that are vital for astrocyte-neuron communication. Therefore, astrocyte dysfunction may contribute to the earliest neuronal deficits in AD. Here we discuss emerging concepts in glial biology and the implications of astrocyte dysfunction on neurodegeneration in AD.
阿尔茨海默病（AD）是由淀粉样蛋白-β（Aβ）的积累引起的，它会导致学习、记忆和其他认知功能的逐渐下降。Aβ是一种神经毒性蛋白，会破坏神经元中的钙信号，并改变突触可塑性。这些影响导致突触丧失、神经网络功能障碍和神经元信号失活。然而，尽管经过几十年的密集研究，Aβ导致神经退行性变的确切机制仍不清楚。星形胶质细胞在早期认知衰退中的作用是疾病病理学的一个主要组成部分，但一直未得到充分理解。最近的研究表明，星形胶质细胞不仅仅是神经元的被动支持细胞，而是大脑中神经信息处理的积极参与者。Aβ可以破坏星形胶质细胞的钙信号和神经递质释放，这些过程对于星形胶质细胞-神经元通讯至关重要。因此，星形胶质细胞功能障碍可能导致 AD 中最早的神经元缺陷。在这里，我们讨论了神经胶质生物学的新兴概念以及星形胶质细胞功能障碍对 AD 中神经退行性变的影响。
