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在一项针对阿尔茨海默病的初步研究中,脑脊液神经元五聚素受体减少与 PET-Aβ 负荷和脑脊液 Aβ 相关。

Decreased cerebrospinal fluid neuronal pentraxin receptor is associated with PET-Aβ load and cerebrospinal fluid Aβ in a pilot study of Alzheimer's disease.

机构信息

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.

Florey Institute, University of Melbourne, Parkville, Australia.

出版信息

Neurosci Lett. 2020 Jul 13;731:135078. doi: 10.1016/j.neulet.2020.135078. Epub 2020 May 23.

Abstract

Multifactorial pathological processes of Alzheimer's disease (AD) begin decades prior to clinical onset. Early identification of patients at risk of developing AD using biomarkers reflecting various aspects of pathogenesis is necessary for prevention and early intervention. Cortical β-amyloid (Aβ) burden assessed by positron emission tomography (PET) or cerebrospinal fluid (CSF) levels of Aβ42 are validated biomarkers for early identification. Recently, alterations in levels of neuronal proteins, neuronal pentraxin receptor (NPTXR) and neurofilament light (NfL), in the CSF have emerged as promising AD biomarkers. However, their association with Aβ deposition is not well understood. In this pilot study, we evaluate whether CSF NfL and NPTXR are associated with PET-Aβ imaging and core CSF biomarkers (Aβ42, T-tau, and P-tau). CSF samples were collected from a sub-cohort of participants from the Australian Imaging Biomarkers and Lifestyle study of aging (AIBL) and categorized as either PET-Aβ positive (n = 15) or negative (n = 15). NPTXR was significantly lower in PET-Aβ positive than negative individuals (p =  0.04), and correlated with Aβ42 (rho = 0.69, p <  0.0001), T-tau (rho = 0.45, p =  0.01), and P-tau (rho = 0.51, p =  0.004). However, CSF NfL was not significantly different between PET-Aβ positive and negative individuals and did not correlate with any of the core CSF biomarkers. Similar associations of NPTXR and the core CSF biomarkers persisted in the cognitively normal individuals. Together, NPTXR concentration in CSF may be more sensitive NfL to identify AD risk during the preclinical stage, warranting further investigation into its contribution to AD pathogenesis.

摘要

阿尔茨海默病(AD)的多因素病理过程始于临床发病前数十年。使用反映发病机制各个方面的生物标志物来早期识别有发生 AD 风险的患者对于预防和早期干预至关重要。正电子发射断层扫描(PET)或脑脊液(CSF)中 Aβ42 水平评估的皮质β-淀粉样蛋白(Aβ)负担是早期识别的验证生物标志物。最近,CSF 中神经元蛋白、神经元五聚素受体(NPTXR)和神经丝轻链(NfL)水平的改变已成为有前途的 AD 生物标志物。然而,它们与 Aβ 沉积的关系尚不清楚。在这项初步研究中,我们评估了 CSF NfL 和 NPTXR 是否与 PET-Aβ 成像和核心 CSF 生物标志物(Aβ42、T-tau 和 P-tau)相关。CSF 样本来自澳大利亚成像生物标志物和生活方式老化研究(AIBL)的亚队列参与者,并分为 PET-Aβ 阳性(n=15)或阴性(n=15)。PET-Aβ 阳性个体的 NPTXR 明显低于阴性个体(p=0.04),并且与 Aβ42(rho=0.69,p<0.0001)、T-tau(rho=0.45,p=0.01)和 P-tau(rho=0.51,p=0.004)相关。然而,PET-Aβ 阳性和阴性个体之间的 CSF NfL 没有显著差异,并且与任何核心 CSF 生物标志物都没有相关性。NPTXR 和核心 CSF 生物标志物的相似关联在认知正常个体中仍然存在。总之,CSF 中的 NPTXR 浓度可能比 NfL 更能敏感地识别临床前阶段的 AD 风险,值得进一步研究其对 AD 发病机制的贡献。

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