Abstract:
: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.
journal_name
Aging Celljournal_title
Aging cellauthors
Blasko I,Stampfer-Kountchev M,Robatscher P,Veerhuis R,Eikelenboom P,Grubeck-Loebenstein Bdoi
10.1111/j.1474-9728.2004.00101.xkeywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
169-76issue
4eissn
1474-9718issn
1474-9726pii
ACE101journal_volume
3pub_type
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