Impaired Innate Immunity Mechanisms in the Brain of Alzheimer’s Disease

International Journal of Molecular Sciences

Robert Veerhuis¹  Federico Licastro²  Ilaria Carbone²  Elisa Porcellini²  Martina Romagnoli² 

[1] Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam UMC, 1105 Amsterdam, The Netherlands;Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy;

关键词: alzheimer’s disease;    viral infection;    antiviral genes;    gene expression;    brain immunity;   

DOI  :  10.3390/ijms21031126

来源: DOAJ

【 摘 要 】

Among environmental factors likely associated with Alzheimer’s disease (AD), persistent virus infections, and age-related progressive decline of immune competence might play a pivotal role. However, AD antimicrobial brain immune responses are poorly investigated. The present study focused on genes involved in antimicrobial defenses, especially against virus infections, in the AD brain. In particular, mRNA levels of IRF7, MED23, IL28B, and IFN-α genes were analyzed in hippocampus and temporal cortex brain samples from AD and non-demented controls. All subjects were also genotyped for APOE ε, IRF7, MED23, and IL28B gene polymorphisms. Most AD patients showed decreased mRNA levels of all investigated genes in the hippocampus and temporal cortex. However, a small group of AD patients showed increased hippocampal mRNA expression of MED23, IL28B, and IFN-α. mRNA levels of MED23, IL28B, IFN-α from the hippocampus and those of MED23 from the temporal cortex were further decreased in APOE ε4 allele AD carriers. Moreover, rs6598008 polymorphism of IRF7 was significantly associated with decreased hippocampal expression of IRF7, MED23, IL28B, and IFN-α. These findings suggest that AD brains show impaired innate antimicrobial gene expression profiles, and individual genetic makeup, such as positivity for the APOE ε4 and IRF7 A alleles, might affect brain immune efficiency.

【 授权许可】

Unknown