How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes.
A huge amount of evidence has implicated amyloid beta (A beta) peptides and other derivatives of the amyloid precursor protein (beta APP) 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-1 beta can then in combination with interferon-gamma be toxic on neurons and affect the metabolism of beta APP 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 A beta can trigger chronic inflammatory processes in microglial cells and astrocytes and thus initiate a vicious circle. This leads to a perpetuation of the disease.
Department of Psychiatry, University Hospital of Innsbruck, Innsbruck, Austria.
Imrich
I
Blasko
Michaela
M
Stampfer-Kountchev
Peter
P
Robatscher
Robert
R
Veerhuis
Piet
P
Eikelenboom
Beatrix
B
Grubeck-Loebenstein
D000375:Aging / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism / Q000502:physiology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000893:Anti-Inflammatory Agents