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脑内基因表达与健康受试者和 AD 患者的认知表现相关。

Brain Expression Correlates with and in Healthy Subjects and AD Patients.

机构信息

Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, 95123 Catania, Italy.

IRCCS Centro Neurolesi Bonino Pulejo, Strada Statale 113, C.da Casazza, 98124 Messina, Italy.

出版信息

Cells. 2021 Apr 13;10(4):882. doi: 10.3390/cells10040882.

DOI:10.3390/cells10040882
PMID:33924468
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8069241/
Abstract

Alzheimer's disease is a progressive, devastating, and irreversible brain disorder that, day by day, destroys memory skills and social behavior. Despite this, the number of known genes suitable for discriminating between AD patients is insufficient. Among the genes potentially involved in the development of AD, there are the chitinase-like proteins (CLPs) CHI3L1, CHI3L2, and CHID1. The genes of the first two have been extensively investigated while, on the contrary, little information is available on CHID1. In this manuscript, we conducted transcriptome meta-analysis on an extensive sample of brains of healthy control subjects (n = 1849) (NDHC) and brains of AD patients (n = 1170) in order to demonstrate CHID1 involvement. Our analysis revealed an inverse correlation between the brain expression levels and the age of NDHC subjects. Significant differences were highlighted comparing CHID1 expression of NDHC subjects and AD patients. Exclusive in AD patients, the expression levels were correlated positively to calcium-binding adapter molecule 1 () levels. Furthermore, both in NDHC and in AD patient's brains, the expression levels were directly correlated with calbindin 1 () and neurogranin (). According to brain regions, correlation differences were shown between the expression levels of in prefrontal, frontal, occipital, cerebellum, temporal, and limbic system. Sex-related differences were only highlighted in NDHC. CHID1 represents a new chitinase potentially involved in the principal processes underlying Alzheimer's disease.

摘要

阿尔茨海默病是一种进行性、破坏性和不可逆转的大脑疾病,它每天都会破坏记忆能力和社交行为。尽管如此,目前已知适合区分 AD 患者的基因数量仍然不足。在可能参与 AD 发展的基因中,有几丁质酶样蛋白 (CLPs) CHI3L1、CHI3L2 和 CHID1。前两个基因已经得到了广泛的研究,而相反,关于 CHID1 的信息却很少。在本文中,我们对大量健康对照组(n=1849)(NDHC)和 AD 患者(n=1170)的大脑进行了转录组元分析,以证明 CHID1 的参与。我们的分析表明,CHID1 的脑表达水平与 NDHC 受试者的年龄呈负相关。比较 NDHC 受试者和 AD 患者的 CHID1 表达水平,突出了显著的差异。在 AD 患者中,表达水平与钙结合适配器分子 1 () 水平呈正相关。此外,在 NDHC 和 AD 患者的大脑中,表达水平与钙结合蛋白 1 () 和神经颗粒蛋白 () 呈直接相关。根据大脑区域,在额前叶、额叶、枕叶、小脑、颞叶和边缘系统中, 表达水平的相关性存在差异。仅在 NDHC 中突出了性别相关差异。CHID1 代表一种新的几丁质酶,可能参与阿尔茨海默病的主要过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/feca/8069241/332dfd29b2be/cells-10-00882-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/feca/8069241/332dfd29b2be/cells-10-00882-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/feca/8069241/327f1242396f/cells-10-00882-g002.jpg
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