Regional Gene Expression of Inflammation and Oxidative Stress Responses Does Not Predict Neurodegeneration in Aging.
Brain aging is accompanied by increased oxidative stress and what has been termed "neuroinflammation," which might contribute to age-related neurodegenerative diseases. We analyzed expression in the transcription of innate inflammatory response genes in eleven representative regions including frontal, parietal, inferior temporal, cingulate, occipital, entorhinal cortex, caudate, putamen, thalamus, substantia nigra, and cerebellar vermis in aging human brains. We probed members of the complement system, colony stimulating factor receptors, toll-like receptors, and pro- and anti-inflammatory cytokines in the brains of subjects with no neurological disease and neurofibrillary tangles (mean age: 47.1  ±  5.7 years) and those with no neurological disease and neurofibrillary pathology stages I-II (mean age: 70.6  ±  6.3 years). Although the entorhinal and frontal cortex were most altered, gene regulation patterns did not match regions with increased vulnerability. Analysis of false discovery rate thresholds revealed no differences for any gene in any region between the 2 groups, including cases in which individual comparisons analyzed using Student t or nonparametric tests showed apparent differences between groups. Moreover, gene expression of major anti-oxidative stress responses did not match neuroinflammation in aging or increased regional susceptibility to major neurodegenerative diseases.
From the Institute of Neuropathology, Service of Pathologic Anatomy, Bellvitge University Hospital (IL-G, IF); Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat (IL-G, CTC, IF); Faculty of Medicine and Health Sciences, University Rovira i Virgili University, Reus (CTC); Department of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat (IF); Institute of Neurosciences, University of Barcelona (IF); and CIBERNED (Biomedical Research Center Network for the Study of Neurodegenerative Diseases, Institute Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain (IF).
Irene
I
López-González
From the Institute of Neuropathology, Service of Pathologic Anatomy, Bellvitge University Hospital (IL-G, IF); Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat (IL-G, CTC, IF); Faculty of Medicine and Health Sciences, University Rovira i Virgili University, Reus (CTC); Department of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat (IF); Institute of Neurosciences, University of Barcelona (IF); and CIBERNED (Biomedical Research Center Network for the Study of Neurodegenerative Diseases, Institute Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain (IF).
Cristian
C
Tebé Cordomí
From the Institute of Neuropathology, Service of Pathologic Anatomy, Bellvitge University Hospital (IL-G, IF); Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat (IL-G, CTC, IF); Faculty of Medicine and Health Sciences, University Rovira i Virgili University, Reus (CTC); Department of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat (IF); Institute of Neurosciences, University of Barcelona (IF); and CIBERNED (Biomedical Research Center Network for the Study of Neurodegenerative Diseases, Institute Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain (IF).
Isidro
I
Ferrer
D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology*; D018384:Oxidative Stress / Q000235:genetics*; D011237:Predictive Value of Tests
D016207:Cytokines
Brain aging; Cytokines; Inflammation; Oxidative stress responses; Regional vulnerability.