In Vivo and Ex Vivo Imaging of Amyloid-β Cascade Aggregates with a Pronucleon™ Peptide
In Vivo and Ex Vivo Imaging of Amyloid-β Cascade Aggregates with a Pronucleon™ Peptide
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DOI：
10.3233/jad-122107
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Rudolph, Alan S.
中科院分区：
文献类型：
--
作者：
Nyborg, Andrew C.;Moll, Jonathan R.;Rudolph, Alan S.
淀粉样β蛋白(Aβ)级联聚集体的积累被认为是阿尔茨海默病(AD)的标志。目前的学说认为，Aβ寡聚体和更大的聚集体的出现早于斑块形成的许多年，与AD晚期和不可修复的神经认知功能下降有关。这一前提是在晚期斑块形成之前识别这些Aβ前体结构的动力。Pronucleon(TM)技术平台由一系列新颖的工程多肽组成，当与富含贝塔的纤维和寡聚体A贝塔结合时，这些多肽提供独特的读数。这项技术已经应用于AD的体外组织切片和体内小鼠模型，以确定这些合成肽作为潜在显像剂的潜在用途。在体外研究中，前核子(TM)肽结合了从过度表达HAPP的转基因小鼠获得的大脑切片中的斑块状结构，这些转基因小鼠同时带有人类瑞典和伦敦Aβ突变。在体内，外周给药的前核子(TM)肽可以定位到大脑，并标记转基因小鼠整个大脑的斑块。综上所述，这些数据表明，Pronucleon(TM)可以为晚期斑块和纤维形成之前的Aβ级联成分提供一种新的成像工具，从而增加早期诊断和治疗的机会。
Accumulation of amyloid-beta (A beta) cascade aggregates is considered a hallmark of Alzheimer's disease (AD). Current dogma holds that the appearance of A beta oligomers and larger aggregates occur many years prior to plaque formation associated with the advanced and irreparable neurocognitive decline characteristic of AD. This premise is the impetus to identify these A beta precursor structures prior to advanced plaque development. The Pronucleon (TM) technology platform is comprised of a novel series of engineered peptides that provide a unique readout when associated with beta-rich fiber and oligomeric A beta. This technology has been applied to ex vivo tissue sections and in vivo mouse models of AD to determine the potential utility of these synthetic peptides as potential imaging agents. In ex vivo studies, the Pronucleon (TM) peptide binds plaque like structures in brain sections obtained from transgenic mice overexpressing hAPP with both the human Swedish and London A beta mutations. In vivo, Pronucleon (TM) peptide administered peripherally can localize to the brain and label plaques throughout the brain in transgenic mice. Taken together, the data suggest that Pronucleon (TM) could provide a new imaging tool for A beta cascade elements that precede advanced plaque and fibril formation, thereby advancing early diagnosis and treatment opportunities.