Low expression of aging-related NRXN3 is associated with Alzheimer disease: A systematic review and meta-analysis.

Abstract:

BACKGROUND:Alzheimer disease (AD) is a common neurodegenerative disorder with distinct pathological features, with aging considered the greatest risk factor. We explored how aging contributes to increased AD risk, and determined concurrent and coordinate changes (including genetic and phenotypic modifications) commonly exhibited in both normal aging and AD. METHODS:Using the Gene Expression Omnibus (GEO) database, we collected 1 healthy aging-related and 3 AD-related datasets of the hippocampal region. The normal aging dataset was divided into 3 age groups: young (20-40 years old), middle-aged (40-60 years old), and elderly (>60 years old). These datasets were used to analyze the differentially expressed genes (DEGs). The Gene Ontology (GO) terms, pathways, and function network analysis of these DEGs were analyzed. RESULTS:One thousand two hundred ninety-one DEGs were found to be shared in the natural aging groups and AD patients. Among the shared DEGs, ATP6V1E1, GNG3, NDUFV2, GOT1, USP14, and NAV2 have been previously found in both normal aging individuals and AD patients. Furthermore, using Java Enrichment of Pathways Extended to Topology (JEPETTO) analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we determined that changes in aging-related KEGG annotations may contribute to the aging-dependence of AD risk. Interestingly, NRXN3, the second most commonly deregulated gene identified in the present study, is known to carry a mutation in AD patients. According to functional network analysis, NRXN3 plays a critical role in synaptic functions involved in the cognitive decline associated with normal aging and AD. CONCLUSION:Our results indicate that the low expression of aging-related NRXN3 may increase AD risk, though the potential mechanism requires further clarification.

journal_name

Medicine (Baltimore)

journal_title

Medicine

authors

Zheng JJ,Li WX,Liu JQ,Guo YC,Wang Q,Li GH,Dai SX,Huang JF

doi

10.1097/MD.0000000000011343

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

e11343

issue

28

eissn

0025-7974

issn

1536-5964

pii

00005792-201807130-00021

journal_volume

97

pub_type

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