Affiliations: [a] Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA | [b] Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA | [c] Department of Neurobiology and Developmental Science, University of Arkansas for Medical Sciences, Little Rock, AR, USA | [d] Department of Physiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA | [e] Geriatric Research Education Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA
Correspondence:
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Corresponding author: W. Sue T. Griffin, PhD, Editor-in-Chief, Journal of Neuroinflammation, Professor and Vice Chairman, Donald W. Reynolds Dept of Geriatrics, University of Arkansas for Medical Sciences, Director of Research, Geriatric Research Education Clinical Center, VAMC/CAVHS, 629 Jack Stephens Dr., Rm 3103, Little Rock, AR 72205, USA. Tel.: +1 501 526 5800; Fax: +1 501
526 5830; E-mail: [email protected].
Abstract: The role of the brain's innate immune system in Alzheimer pathogenesis is now well established. Proinflammatory cytokines elaborated by this system, in particular activated microglia-derived interleukin-1 (IL-1), drive a cascade of neurotoxic changes that are important for the development and progression of both the neuritic plaques and neurofibrillary tangles characteristic of Alzheimer's disease. Cytokine expression may also be modulated by variants of genes. For instance, inheritance of certain IL-1 gene variants is associated with Alzheimer's disease. The potential for using blood levels of proinflammatory cytokines as biomarkers of disease progression, however, remains unrealized. The interpretation of cytokine levels in the blood is complicated by the fact, for example, that the overexpression of IL-1 in Alzheimer brain may act to increase adrenal cortisol production through the hypothalamic-pituitary-adrenal axis, which acts to limit macrophage activation and peripheral cytokine production.
