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

• Published in: International journal of molecular sciences Vol. 21; no. 3; p. 1126
• Main Authors: Romagnoli, Martina, Porcellini, Elisa, Carbone, Ilaria, Veerhuis, Robert, Licastro, Federico
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.02.2020; MDPI
• Subjects: Aged; Aged, 80 and over; Aging; Alleles; Alzheimer Disease - genetics; Alzheimer Disease - immunology; Alzheimer Disease - metabolism; Alzheimer's disease; Antiinfectives and antibacterials; Antimicrobial agents; antiviral genes; Apolipoprotein E; Brain; Brain - metabolism; Brain - pathology; brain immunity; Efficiency; Epstein-Barr virus; Female; Gene expression; Gene polymorphism; Genes; Herpes viruses; Hippocampus; Hippocampus - metabolism; Humans; Immune response; Immune system; Immunity (Disease); Immunity, Innate - genetics; Immunity, Innate - physiology; Infections; Innate immunity; Interferon regulatory factor 7; Interferon Regulatory Factor-7 - genetics; Interferon Regulatory Factor-7 - metabolism; Interferon-alpha - genetics; Interferon-alpha - metabolism; Interferons - genetics; Interferons - metabolism; Male; Mediator Complex - genetics; Mediator Complex - metabolism; Middle Aged; Neurodegeneration; Pathogens; Peptides; Polymorphism; RNA polymerase; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal transduction; Temporal lobe; viral infection; Viral infections; α-Interferon; viral infection; Alzheimer’s disease; brain immunity; antiviral genes; gene expression
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21031126

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.