Inflammatory proteins may slow cognitive decline, study finds
Elevated levels of two chemical mediators of inflammation, known as cytokines, are associated with slower cognitive decline in aging adults, according to new research from Massachusetts General Hospital (MGH) and the Harvard Aging Brain Study (HABS) published in the journal Alzheimer's & Dementia.
Research has previously linked inflammation to Alzheimer's disease (AD). However, the new results are unexpected, said the study’s co-senior author Rudolph Tanzi, PhD, vice chair of Neurology and co-director of the Henry and Allison McCance Center for Brain Health at MGH. These findings could eventually be used to help identify healthy people who are at risk for the devastating neurological condition, before they have symptoms, he said.
In 2008, Tanzi led a team that discovered CD33, the first AD gene associated with the immune system, the body's defense network that fights infection. Since then, most new AD genes identified have been linked to the immune system, and many studies support the theory that immune system dysfunction plays a part in AD. Notably, research has shown that people with AD and other forms of dementia have elevated levels of certain cytokines.
However, until now the role of the immune system in the earliest stage of AD, when brain changes characteristic of the disease silently progress in older adults without cognitive symptoms, was unclear.
In the new study, Tanzi and his team collaborated with HABS investigators to find out if measuring cytokines in the blood—instead of in cerebrospinal fluid, which requires a lumbar puncture procedure, or spinal tap—could help predict which healthy people will later experience cognitive decline. Of particular interest were older people with normal cognition, but who had undergone imaging tests and were found to have deposits of amyloid beta, the major component of amyloid plaques, which are associated with AD, in their brains.
The new study included 298 men and women from HABS, who were between the ages 50 and 90. All had normal cognitive abilities when they volunteered and undergo retesting annually. Upon joining HABS, all participants had blood samples taken and underwent positron emission tomography (PET) brain-imaging scans. Among other things, these scans looked for evidence of amyloid beta and other changes associated with AD, such as formations called tau tangles.
The study screened each participant's blood for nine cytokines to see if any were associated with the rate of cognitive decline and changes in the brain. The study found that people whose brains had a significant burden of amyloid beta, but who also had high levels of a pro-inflammatory cytokine called interleukin-12 (IL-12), experienced little cognitive decline.
While it may seem counterintuitive that people who were protected against cognitive decline had the highest levels of inflammation-inducing proteins in the blood, that may be an indication that their immune systems were better "primed" to fight infection, said Tanzi. These results suggest that IL-12 and IFN-γ could one day be measured along with other biomarkers to predict future brain health in cognitively normal people, a tool that doesn't yet exist in medicine.
"We don't have a 'checkup from the neck up'," he said. “The next step toward that goal will be studying how IL-12 and IFN-γ may ward off cognitive decline and promote healthy brain aging.”