Free Content How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes

Authors: Imrich Blasko1; Michaela Stampfer-Kountchev2; Peter Robatscher2; Robert Veerhuis3; Piet Eikelenboom3; Beatrix Grubeck-Loebenstein

Source: Aging Cell, Volume 3, Number 4, August 2004 , pp. 169-176(8)

Publisher: Blackwell Publishing

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Abstract:

Summary

A huge amount of evidence has implicated amyloid beta (Abgr) peptides and other derivatives of the amyloid precursor protein (bgrAPP) as central to the pathogenesis of Alzheimer's disease (AD). It is also widely recognized that age is the most important risk factor for AD and that the innate immune system plays a role in the development of neurodegeneration. Little is known, however, about the molecular mechanisms that underlie age-related changes of innate immunity and how they affect brain pathology. Aging is characteristically accompanied by a shift within innate immunity towards a pro-inflammatory status. Pro-inflammatory mediators such as tumour necrosis factor-alpha or interleukin-1bgr can then in combination with interferon-ggr be toxic on neurons and affect the metabolism of bgrAPP such that increased concentrations of amyloidogenic peptides are produced by neuronal cells as well as by astrocytes. A disturbed balance between the production and the degradation of Abgr can trigger chronic inflammatory processes in microglial cells and astrocytes and thus initiate a vicious circle. This leads to a perpetuation of the disease.

Keywords: aging; Alzheimer's disease; amyloid beta; astrocytes; innate immune system; microglial cells

Document Type: Research article

DOI: 10.1111/j.1474-9728.2004.00101.x

Affiliations: 1: Department of Psychiatry, University Hospital of Innsbruck, Innsbruck, Austria 2: Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria 3: Department of Psychiatry and Pathology, Research Institute of Neurosciences, Vrije Universiteit Amsterdam, The Netherlands

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