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Established genetic causes of familial Alzheimer disease (AD) involve genes for [beta]-amyloid precursor protein ([beta]APP), presenilin-1, and presenilin-2. For the more common sporadic forms of AD, increased risk has been associated with a number of genes; the most important of which is the [epsilon]4 allele of apolipoprotein E. Two recent studies, one clinical and one using postmortem material, now show increased risk for AD associated with certain polymorphisms in the genes encoding the [alpha] and [beta] isoforms of interleukin-1 (IL-1). IL-1 levels are elevated in Alzheimer brain, and overexpression of IL-1 is associated with [beta]-amyloid plaque progression. IL-1 interacts with the gene products of several other known or suspected genetic risk factors for AD, including [beta]APP, apolipoprotein E, [alpha]1-antichymotrypsin, and [alpha]2-macroglobulin. IL-1 overexpression is also associated with environmental risk factors for AD, including normal aging and head trauma. These observations suggest an important pathogenic role for IL-1, and for IL-1-driven cascades, in the pathogenesis of AD.

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