Alzheimer's disease: are blood and brain markers related? A systematic review.
Alzheimer's disease: are blood and brain markers related? A systematic review.
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DOI：
10.1002/acn3.313
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发表时间：
2016-06
影响因子：
5.3
通讯作者：
Kiddle SJ
中科院分区：
文献类型：
--
作者：
Khan AT;Dobson RJ;Sattlecker M;Kiddle SJ
阿尔茨海默病（AD）的外周蛋白生物标志物可以通过早期诊断、临床试验招募和治疗启动来帮助确定新的治疗途径。本综述的目的是确定哪些蛋白质在阿尔茨海默病患者的大脑中被发现有差异表达，以及这些蛋白质是否也存在于阿尔茨海默病患者的血液中。采用两阶段方法。第一阶段涉及进行系统搜索，以确定基于发现的AD脑蛋白质组学研究。第二阶段涉及比较在AD大脑中发现的差异表达的蛋白质是否在血液中也有差异表达。在11项基于发现的大脑蛋白质组学研究中，有371种蛋白质在阿尔茨海默氏症患者的大脑中处于不同的水平。九种蛋白质经常被发现，被定义为出现在至少三个独立的研究中。在这些热休克同源蛋白71 kDa中，发现泛素羧基末端水解酶同工酶L1和2′，3′环核苷酸3′磷酸二酯酶单独具有一致的变化方向，在它们出现的研究中一致上调。在阿尔茨海默病的血液蛋白质组学研究中，有18种蛋白质在阿尔茨海默病大脑中被认为是差异表达的。只有补体C4a在血液和脑蛋白质组学研究中被多次观察到。我们报道了一些蛋白质出现在阿尔茨海默病患者的血液和大脑中。在这些蛋白中，C4a可能是进一步大规模复制的良好候选蛋白。
Peripheral protein biomarkers of Alzheimer's disease (AD) may help identify novel treatment avenues by allowing early diagnosis, recruitment to clinical trials, and treatment initiation. The purpose of this review was to determine which proteins have been found to be differentially expressed in the AD brain and whether these proteins are also found within the blood of AD patients. A two‐stage approach was conducted. The first stage involved conducting a systematic search to identify discovery‐based brain proteomic studies of AD. The second stage involved comparing whether proteins found to be differentially expressed in AD brain were also differentially expressed in the blood. Across 11 discovery based brain proteomic studies 371 proteins were at different levels in the AD brain. Nine proteins were frequently found, defined as appearing in at least three separate studies. Of these proteins heat‐shock cognate 71 kDa, ubiquitin carboxyl‐terminal hydrolase isozyme L1, and 2′,3′‐cyclic nucleotide 3′ phosphodiesterase alone were found to share a consistent direction of change, being consistently upregulated in studies they appeared in. Eighteen proteins seen as being differentially expressed within the AD brain were present in blood proteomic studies of AD. Only complement C4a was seen multiple times within both the blood and brain proteomic studies. We report a number of proteins appearing in both the blood and brain of AD patients. Of these proteins, C4a may be a good candidate for further follow‐up in large‐scale replication efforts.