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Review
, 35 (4), 481-7

The Pervasiveness of interleukin-1 in Alzheimer Pathogenesis: A Role for Specific Polymorphisms in Disease Risk

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Review

The Pervasiveness of interleukin-1 in Alzheimer Pathogenesis: A Role for Specific Polymorphisms in Disease Risk

W S Griffin et al. Exp Gerontol.

Abstract

Interleukin-1 (IL-1) has been implicated as a key molecule in Alzheimer pathogenesis based on findings of an IL-1 overexpression in Alzheimer brain that is directly related to plaque progression and tangle formation, and on findings that IL-1 induces excessive synthesis, translation, and processing of neuronal beta-amyloid precursor protein (betaAPP) as well as synthesis of most known plaque-associated proteins. In addition, IL-1 activates astrocytes, with the important consequence of overexpression of the neuritogenic cytokine S100beta and overgrowth of dystrophic neurites in neuritic plaques. As further evidence of the importance of IL-1 in Alzheimer pathogenesis, two new genetic studies of inheritance of specific polymorphisms in IL-1 genes in Alzheimer and control patients show that homozygosity for a specific IL-1A gene polymorphism at least triples risk for development of Alzheimer's disease. This increase is associated with earlier age of onset. Homozygosity for this polymorphism plus another in the IL-1B gene further increases risk.

Figures

Fig. 1
Fig. 1
This is a schematic diagram demonstrating pathogenesis of neuritic plaque as a consequence of neuronal injury, activation of microglia with overexpression of IL-1, and subsequent initiation of IL-1 driven cascades. (A), (B), and (C) represent progressive stages of β-amyloid plaque evolution.

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