Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice
Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice
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DOI：
10.1016/j.neurobiolaging.2004.06.010
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发表时间：
2005-05-01
影响因子：
4.2
通讯作者：
Jucker, M
中科院分区：
文献类型：
--
作者：
Boncristiano, S;Calhoun, ME;Jucker, M
阿尔茨海默病（AD）大脑的主要病理学发现包括β淀粉样蛋白的沉积和突触损失。突触丧失已被证明与 AD 患者的认知能力下降相关，但由于 AD 大脑中神经原纤维缠结和其他病变的存在，脑淀粉样变性和突触丧失之间的关系变得复杂。通过使用过度表达具有瑞典双突变的人类淀粉样前体蛋白（APP）的APP23转基因小鼠模型，我们研究了皮质淀粉样蛋白沉积的发展是否伴随着突触布顿损失。通过体视学方法，我们发现，尽管存在与年龄相关的皮质淀粉样蛋白沉积以及相关的突触变性，但与 3、8 和 15 个月大的 APP23 小鼠相比，24 个月大的动物中皮质突触素阳性突触前末梢的总数没有变化。野生型小鼠的新皮质中也没有表现出与年龄相关的突触前神经元损失，并且与 APP23 小鼠没有显着差异。突触素蛋白质印迹显示 APP23 小鼠和野生型对照小鼠在 3 个月和 25 个月龄时没有显着差异。我们的结果表明，脑淀粉样变性不足以解释 AD 中的整体突触损失。或者，APP 的假定营养作用可以防止、补偿或延迟该小鼠模型中突触的损失。 (C) 2004 Elsevier Inc. 保留所有权利。
Major pathological findings in Alzheimer's disease (AD) brain include the deposition of amyloid-beta and synapse loss. Synaptic loss has been shown to correlate with the cognitive decline in AD patients, but the relationship between cerebral amyloidosis and synapse loss is complicated by the presence of neurofibrillary tangles and other lesions in AD brain. With the use of the APP23 transgenic mouse model that overexpresses human amyloid precursor protein (APP) with the Swedish double mutation, we investigated whether the development of cortical amyloid deposition was accompanied by synaptic bouton loss. With stereological methods, we show that despite robust age-related cortical amyloid deposition with associated synaptic degeneration, the total number of cortical synaptophysin-positive presynaptic terminals is not changed in 24-month-old animals compared with 3-, 8-, and 15-month-old APP23 mice. Wild-type mice also do not show an age-related loss of presynaptic boutons in the neocortex and are not significantly different from APP23 mice. Synaptophysin Western blotting revealed no significant difference between APP23 mice and wild-type controls at 3 and 25 months of age. Our results suggest that cerebral amyloidosis is not sufficient to account for the global synapse loss in AD. Alternatively, a putative trophic effect of APP may prevent, compensate, or delay a loss of synapses in this mouse model. (C) 2004 Elsevier Inc. All rights reserved.