01 Mar 2000

For more than a decade, a case has been building for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease. Now researchers say they have found definitive evidence that implicates the inflammatory cytokine interleukin-1 (IL-1). In this month's Annals of Neurology, two groups have published evidence that common variations in the genes that code for IL-1 are associated with increased risk for Alzheimer's, and particularly for early onset Alzheimer's.

Interleukin-1 is produced by two genes, IL-1A and IL-1B, each of which has several polymorphisms (configurational variations common in the population). Luigi Grimaldi and his colleagues in Italy and the United States tested DNA from living patients who had been clinically diagnosed with Alzheimer's (and from case-matched controls). They found that homozygote carriers of the IL-1A polymorphism termed allele 2 had twice the risk of getting Alzheimer's as those who did not have this polymorphism. Moreover, Grimaldi said, "When we looked only at patients with Alzheimer's disease, we found that this particular configuration of IL-1A was associated five times more frequently with an onset of disease before 65 years of age." Patients homozygous for the allele 2 polymorphism developed the disease an average of nine years earlier than patients who did not have that polymorphism.

In a separate paper, Sue Griffin of the Veterans Affairs Medical Center in Little Rock, Arkansas, and her colleagues report that they found (in autopsy tissue from confirmed Alzheimer's cases and case-matched controls) a threefold increased risk for Alzheimer's in people homozygous for IL-1A allele 2. They also found that people homozygous for allele 2 of both IL-1A and IL-1B stood 10 times the risk of getting Alzheimer's compared with those who had neither of these polymorphisms. Griffin expects these data to be confirmed soon by the publication of similar results in other patient populations.

Grimaldi speculates that Alzheimer's might be delayed in some patients just by prescribing a couple of aspirin a day, and he suggests that pilot clinical trials in humans are warranted.—Hakon Heimer

(See also an editorial by Rudy Tanzi in the same issue discussing these results.)