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唐氏综合征患者在出现临床阿尔茨海默病前后的神经生长因子（NGF）通路生物标志物：一项配对的 CSF 和血浆研究。

Nerve growth factor (NGF) pathway biomarkers in Down syndrome prior to and after the onset of clinical Alzheimer's disease: A paired CSF and plasma study.

机构信息

Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.

Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.

出版信息

Alzheimers Dement. 2021 Apr;17(4):605-617. doi: 10.1002/alz.12229. Epub 2020 Nov 23.

DOI:10.1002/alz.12229
PMID:33226181
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8043977/
Abstract

BACKGROUND

The discovery that nerve growth factor (NGF) metabolism is altered in Down syndrome (DS) and Alzheimer's disease (AD) brains offered a framework for the identification of novel biomarkers signalling NGF deregulation in AD pathology.

METHODS

We examined levels of NGF pathway proteins (proNGF, neuroserpin, tissue plasminogen activator [tPA], and metalloproteases [MMP]) in matched cerebrospinal fluid (CSF)/plasma samples from AD-symptomatic (DSAD) and AD-asymptomatic (aDS) individuals with DS, as well as controls (HC).

RESULTS

ProNGF and MMP-3 were elevated while tPA was decreased in plasma from individuals with DS. CSF from individuals with DS showed elevated proNGF, neuroserpin, MMP-3, and MMP-9. ProNGF and MMP-9 in CSF differentiated DSAD from aDS (area under the curve = 0.86, 0.87). NGF pathway markers associated with CSF amyloid beta and tau and differed by sex.

DISCUSSION

Brain NGF metabolism changes can be monitored in plasma and CSF, supporting relevance in AD pathology. These markers could assist staging, subtyping, or precision medicine for AD in DS.

摘要

背景

神经生长因子（NGF）代谢在唐氏综合征（DS）和阿尔茨海默病（AD）大脑中发生改变的发现，为鉴定 AD 病理中 NGF 失调的新型生物标志物提供了框架。

方法

我们检测了匹配的 AD 症状性（DSAD）和 AD 无症状（aDS）DS 个体以及对照者（HC）的脑脊液（CSF）/血浆样本中 NGF 通路蛋白（proNGF、神经丝氨酸蛋白酶抑制剂、组织型纤溶酶原激活物 [tPA] 和金属蛋白酶 [MMP]）的水平。

结果

DS 个体的血浆中 proNGF 和 MMP-3 升高，而 tPA 降低。DS 个体的 CSF 中 proNGF、神经丝氨酸蛋白酶抑制剂、MMP-3 和 MMP-9 升高。CSF 中的 proNGF 和 MMP-9 可区分 DSAD 和 aDS（曲线下面积分别为 0.86、0.87）。与 CSF 淀粉样β和 tau 相关的 NGF 通路标志物存在性别差异。

讨论

大脑 NGF 代谢变化可在血浆和 CSF 中监测，支持其在 AD 病理中的相关性。这些标志物可辅助 AD 患者的分期、亚型分类或精准医疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/c21f59e9cb22/ALZ-17-605-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/7ab9f8048d92/ALZ-17-605-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/a7562e81e36f/ALZ-17-605-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/ece4c663acfc/ALZ-17-605-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/afac8fbf10a7/ALZ-17-605-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/c21f59e9cb22/ALZ-17-605-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/7ab9f8048d92/ALZ-17-605-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/a7562e81e36f/ALZ-17-605-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/ece4c663acfc/ALZ-17-605-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/afac8fbf10a7/ALZ-17-605-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4cc/8247397/c21f59e9cb22/ALZ-17-605-g005.jpg

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