University of Arkansas professor Sue T Griffin has been a pioneer in Alzheimer’s disease research. In the mid-1980s Griffin was doing research in developmental neurobiology at the University of Texas Health Science Center in Dallas, when she noticed that the brains of patients with Alzheimer's disease and Down's syndrome had a similar excess of cytokines, immune signal proteins that cause inflammation and – sometimes – the death of neighboring neurons. She speculated that Alzheimer's disease occurs because of a cycle of cytokine-induced events in the brain, beginning with the release of amyloid, a protein fragment that is deposited as plaques, triggering release of more of these inflammatory cytokines. Interleukin-1 (IL-1) is chief among these cytokines and has subsequently been shown to cause further release of the plaque components, thereby propagating damage to an ever-expanding area of the brain.
Griffin wondered if an excess of the cytokines in the brain fostered the development of Alzheimer's, and if the gene that produced that excess could be identified, could scientists "catch" Alzheimer's early enough to prevent it? This idea was a departure from the conventional wisdom about Alzheimer's disease. The leading researchers in the field, were focusing on the hypothesis that amyloid plaques were themselves directly responsible for damage to neurons.
After moving to Arkansas in 1986 as a professor in the Department of Pediatrics at the University of Arkansas for Medical Sciences (UAMS) College of Medicine, Dr. Griffin and her collaborators at UAMS first established in 1989 that Interleukin-1 is, indeed, over-expressed in the brains of persons with Alzheimer's disease. Just as importantly, they showed that IL-1 is over-expressed throughout the progression from Down's syndrome to Alzheimer's disease. (Persons with Down's syndrome typically develop Alzheimer's disease in later life.) Dr. Griffin and her colleagues reported the "cytokine cycle" in 1992. Next, they identified the variants of IL-1 genes that are associated with over-expression of the cytokine, B-amyloid precursor protein, the potential linchpin in the cytokine cycle, in 2000. Today a fairly rapid and inexpensive blood test can reveal the presence of those variants of IL-1.
Dr. Griffin and others also have shown that the over-expression of IL-1 can trigger several phenomena related to Alzheimer's disease. Scientists at several other universities have confirmed their discovery. Their findings were very exciting because IL-1 can be regulated with readily-available drugs.
Scientists now widely accept the theory that this chronic inflammatory response in the brain is an important factor in the development of Alzheimer's disease. In recent years other scientists have confirmed in multiple studies that individuals who take anti-inflammatory drugs regularly for other conditions are much less likely to develop the disease than individuals who do not take the drugs. Even more convincing, Dr. Griffin and her collaborators were able to show that people who have certain DNA sequences in the gene for interleukin-1 are more likely to get Alzheimer's disease. This finding was convincing evidence that interleukin-1 is a key factor in development of the disease.
Dr. Griffin is currently focusing on how these discoveries can help physicians stop Alzheimer's disease before its effects are severe. "Our idea is to detect the disease as early as possible and then intervene with drug therapies or alternative treatments before it reaches its very degenerative stages, so we can keep people functionally independent," she explains. Functional genomics will be used to determine how interleukin-1 gene variations alter inflammation in the brain, leading to Alzheimer's disease. Genomics is a discipline that identifies genes, their interactions, and their effects on biological processes. It promises to accelerate the development of new approaches to treating human diseases. This information, together with other genetic data, will be used to develop new drug therapies for individuals who have an over-expression of Interleukin-1.
The National Institutes of Health (NIH) recently awarded her and her colleagues at the University of Arkansas for Medical Sciences (UAMS) another $7 million to continue her work on Alzheimer's disease and related problems of aging.