Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.
Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.
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DOI：
10.1016/j.nbd.2018.02.014
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发表时间：
2018-06
影响因子：
6.1
通讯作者：
Cole GM
中科院分区：
文献类型：
--
作者：
Ma QL;Teng E;Zuo X;Jones M;Teter B;Zhao EY;Zhu C;Bilousova T;Gylys KH;Apostolova LG;LaDu MJ;Hossain MA;Frautschy SA;Cole GM
突触神经变性被认为是由可溶性β - 淀粉样蛋白（Aβ）聚集体引发的早期事件，它与阿尔茨海默病（AD）的认知衰退密切相关。载脂蛋白ε4（APOE4）是家族性阿尔茨海默病（FAD）和散发性阿尔茨海默病最常见的遗传风险因素；它加速Aβ聚集，并选择性地损害谷氨酸受体功能和突触可塑性。然而，其分子机制仍然难以捉摸，并且这些突触缺陷难以监测。已经提出了依赖于AD和APOE4的血浆生物标志物，但缺乏与突触相关的血浆生物标志物。我们评估了神经元正五聚蛋白1（NP1），它是一种潜在的源于中枢神经系统的兴奋性突触病理学血浆生物标志物。NP1在大脑中优先表达，并参与谷氨酸受体内化。NP1由Aβ寡聚体诱导在突触前分泌，并与兴奋性突触和线粒体缺陷有关。在7 - 8个月大的E4FAD小鼠的大脑和血浆中，NP1及其片段的水平相对于E3FAD小鼠以相关的方式增加。NP1也在外泌体制备物中被发现，并且通过膳食补充二十二碳六烯酸（DHA）而减少。相对于E4FAD -（非携带者；APOE4 + / + / FAD - / -）小鼠，E4FAD +（APOE4 + / + / FAD + / -）小鼠的血浆NP1更高，这表明NP1受Aβ表达的调节。最后，相对于正常老年人，轻度认知障碍（MCI）患者的血浆NP1也升高，并且在进展为早期AD的亚组中进一步升高。在这些患者中，APOE4携带者相对于非携带者有NP1水平升高的趋势。这些发现表明，NP1可能代表一种潜在的源于突触的血浆生物标志物，与MCI和早期AD中兴奋性突触的早期改变相关。
Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7–8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4+/+/FAD+/−) relative to E4FAD- (non-carrier; APOE4+/+/FAD−/−) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD.
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影响因子：
6.1
作者：
Al Rahim M;Thatipamula S;Hossain MA
通讯作者：
Hossain MA
影响因子：
34.7
作者：
Bu, Guojun
通讯作者：
Bu, Guojun
影响因子：
3.6
作者：
Enguita, M;DeGregorio-Rocasolano, N;Trullas, R
通讯作者：
Trullas, R
影响因子：
5.3
作者：
Abad, Maria A.;Enguita, Marta;Trullas, Ramon
通讯作者：
Trullas, Ramon
影响因子：
4.2
作者：
Frautschy, SA;Hu, W;Cole, GM
通讯作者：
Cole, GM