Altered expression of amyloid beta precursor mRNAs in cerebral vessels, meninges, and choroid plexus in Alzheimer's disease.
Altered expression of amyloid beta precursor mRNAs in cerebral vessels, meninges, and choroid plexus in Alzheimer's disease.
复制标题
阿尔茨海默病脑血管、脑膜和脉络丛中淀粉样蛋白 β 前体 mRNA 的表达发生改变。
DOI：
10.1111/j.1749-6632.1996.tb34434.x
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发表时间：
1996
影响因子：
5.2
通讯作者：
Kalaria,RN
中科院分区：
文献类型：
--
作者：
Premkumar,DR;Kalaria,RN
淀粉样前体蛋白（APP）的组织特异性加工或产生的改变被认为是阿尔茨海默病（AD）脑血管和新皮质组织中淀粉样蛋白沉积的核心。我们证明，与年龄匹配的对照组相比，AD受试者尸检时获得的脑血管、脑膜和脉络丛中的Aβ肽很容易检测到并增加。使用逆转录（RT）-聚合酶链反应（PCR），我们进一步发现，在AD受试者的血管样本中，编码所有形式APP（包含APP 770的外显子16和17）中Aβ序列的Aβ转录物显著增加。这在新皮质样本中也很明显，与死前因素或死后间隔无关。Aβ mRNA的增加可能反映了白细胞和神经胶质细胞中表达的L-APP亚型（不含外显子15的APP 770）的表达增强。我们还发现，与对照组相比，AD受试者脑血管样本中APP 770、756和695 mRNA的比例发生了变化。而APP 770和APP 751，主要形式，显着减少，APP 695转录增加血管样本AD。这种变化在来自同一受试者的新皮层样本中并不明显。这些观察结果表明，APP亚型表达的组织特异性变化涉及AD脑血管组织中Aβ蓄积增加的机制之一。
Altered tissue‐specific processing or production of the amyloid precursor protein (APP) is thought to be central to amyloid deposition in cerebrovascular and the neocortical tissues in Alzheimer's disease (AD). We demonstrate that Aβ peptide(s) is readily detectable and increased in cerebral vessels, meninges and choroid plexus obtained at autopsy from AD subjects compared to age‐matched controls. Using the reverse transcription (RT)‐polymerase chain reaction (PCR), we further found that Aβ transcripts encoding the Aβ sequence in all forms of APP containing exons 16 and 17 (of APP770) were significantly increased in vessel samples in AD subjects. This was also evident in the neocortical samples and not related to pre‐mortem factors or postmortem interval. It is possible that the increased Aβ mRNAs reflect enhanced expression of the L‐APP isoform (APP770 without exon 15) expressed in leukocytes and glia alike. We also found evidence for changed proportions of APP 770, 756 and 695 mRNAs in cerebral vessel samples from AD subjects compared to controls. Whereas APP770 and APP751, the predominant forms, were significantly decreased, APP695 transcript was increased in vessel samples from AD subjects. Such changes were not evident in neocortical samples from the same subjects. These observations suggest tissue‐specific changes in expression of APP isoforms implicating one of the mechanisms for increased accumulation of Aβ in cerebrovascular tissues in AD.