Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Dept. of Psychiatry and Neurochemistry The Sahlgrenska Academy at the University of Gothenburg Sahlgrenska University Hospital, Mölndal SE-431 80 Mölndal, Sweden.
Curr Pharm Des. 2011;17(25):2594-602. doi: 10.2174/138161211797416039.
The last decades have witnessed an explosion in studies of the role of amyloid-β (Aβ) in the progress of the neurodegenerative disorder Alzheimer's disease (AD) and it is now widely accepted that Aβ is related to the pathogenesis of AD. For example, studies have shown that Aβ is neurotoxic and that the neurotoxicity of Aβ is related to its aggregation state. The concentration of the 42 amino acid form of Aβ (Aβ1-42) is reduced in the cerebrospinal fluid (CSF) from AD patients, which is believed to reflect the AD pathology with plaques in the brain acting as sinks. Less well investigated, however, is the ability of other Aβ isoforms to distinguish AD patients from controls and to identify treatment effects in clinical trials. Recently, novel C-truncated forms of Aβ (Aβ1-14, Aβ1-15, and Aβ1-16) were identified in human CSF. The presence of these small peptides is consistent with a catabolic amyloid precursor protein cleavage pathway by β- followed by α-secretase. It has been shown that Aβ1-14, Aβ1-15, and Aβ1-16 increase dose-dependently in response to γ-secretase inhibitor treatment while Aβ1-42 levels are unchanged. Here, we review the many aspects of Aβ and its isoforms with special focus on their potential role as diagnostic and theragnostic markers.
过去几十年见证了对淀粉样蛋白-β（Aβ）在神经退行性疾病阿尔茨海默病（AD）进展中作用的研究爆炸，现在广泛认为 Aβ 与 AD 的发病机制有关。例如，研究表明 Aβ 具有神经毒性，Aβ 的神经毒性与其聚集状态有关。AD 患者脑脊液（CSF）中 42 个氨基酸形式的 Aβ（Aβ1-42）浓度降低，这被认为反映了大脑斑块作为汇点的 AD 病理学。然而，其他 Aβ 异构体区分 AD 患者和对照组的能力以及在临床试验中识别治疗效果的能力研究得还不够充分。最近，在人类 CSF 中鉴定出新型 C 端截断形式的 Aβ（Aβ1-14、Aβ1-15 和 Aβ1-16）。这些小肽的存在与β-随后的 α-分泌酶的淀粉样前体蛋白裂解途径一致。已经表明，Aβ1-14、Aβ1-15 和 Aβ1-16 随着 γ-分泌酶抑制剂治疗而剂量依赖性增加，而 Aβ1-42 水平不变。在这里，我们特别关注它们作为诊断和治疗标志物的潜在作用，综述了 Aβ 及其异构体的许多方面。
