Bayer T A, Wirths O
Division of Molecular Psychiatry, Department of Psychiatry, University of Goettingen, Goettingen, Germany.
Genes Brain Behav. 2008 Feb;7 Suppl 1:6-11. doi: 10.1111/j.1601-183X.2007.00372.x.
Accumulating evidence points to an important role of intraneuronal Abeta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of Abeta instead of extracellular Abeta deposition has been introduced to be the disease-triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal Abeta42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time-point, a dramatic, age-dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss.
越来越多的证据表明，神经元内β淀粉样蛋白（Aβ）作为导致神经退行性变并最终发展为具有典型临床症状（如记忆障碍和人格改变）的阿尔茨海默病（AD）的病理事件级联反应的触发因素，起着重要作用。作为一个新概念，Aβ在神经元内的积累而非细胞外Aβ沉积已被认为是AD中引发疾病的事件。本综述汇集了关于淀粉样前体蛋白（APP）/早老素1基因敲入（PS1KI）小鼠模型的现有知识，该模型中神经元内早期大量积累Aβ42：（1）APP/PS1KI小鼠模型表现出早期强烈的脑和脊髓轴突变性以及海马CA1神经元丢失。（2）在同一时间点，观察到执行工作记忆和运动任务的能力显著下降，且与年龄相关。（3）APP/PS1KI小鼠体型较小，出现胸腰椎后凸，体重逐渐减轻。（4）观察到的行为改变的起始与脑和脊髓中强烈的轴突变性以及大量海马CA1神经元丢失密切相关。
