Some Causes of Inflammation May Protect Against Cognitive Decline

Some Causes of Inflammation May Protect Against Cognitive Decline

Researchers based at Harvard Medical School have discovered that, contrary to previous findings and expectations, some inflammatory proteins may actually be protective against diseases such as Alzheimer’s and dementia.

The team, co-led by Jasmeer Chhatwal and Rudolph Tanzi, both neurologists and researchers at Massachusetts General Hospital and Harvard Medical School, found that higher levels of two inflammatory cytokines –interferon gamma and interleukin (IL)-12p70– seemed to actively slow cognitive decline in elderly individuals.

“We wanted to know why some people have amyloid in their brain and don’t seem to be affected, while other people experience cognitive decline,” said Chhatwal in a press statement. “These are totally unexpected results,” added Tanzi.

Inflammation and immune dysregulation have been linked to Alzheimer’s disease in the past. But it was previously thought that high levels of inflammatory proteins were causing or contributing to cognitive decline, not protecting against it.

The study had a longitudinal design with 6 years of data. It followed up 298 elderly individuals, aged an average of 72 years on enrollment, with no initial cognitive decline who were participating in the Harvard Aging Brain Study.

The researchers measured levels of 9 different cytokines –interferon gamma, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13,and tumor necrosis factor alpha–  in the participants over time and assessed links with cognitive decline or levels of amyloid beta build up, a common observation in Alzheimer’s patients.

In patients with higher levels of amyloid beta, IL-12p70 appeared to have a protective effect and individuals with high amyloid beta and high IL-12p70 showed significantly less cognitive decline, tau build up and neurodegeneration than those with high levels of amyloid beta alone.

In addition, high levels of interferon gamma were linked with slower cognitive decline regardless of amyloid beta levels.

“These results illustrate the importance of measuring a comprehensive panel of cytokines and interpreting the data with a more nuanced pathway-specific framework rather than relying on a simplified pro- or anti-inflammatory classification,” write the authors in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

The researchers think their findings could fit with the “antimicrobial protection hypothesis” of Alzheimer’s disease, which suggests that build up of amyloid beta can occur in response to a low-level microbial infection in the brain.

“Amyloid beta is thought to function as an antimicrobial peptide that is seeded by microbes to form toxic oligomers that trap pathogens and protect host cells,” write the researchers.

“Thus, one can speculate that higher levels of plasma IL-12 and IFN-γ leading to greater protection from peripheral infection, may also protect against entry of pathogens into the brain, for example in older individuals with reduced blood-brain barrier integrity.”

The team acknowledges that further validation and testing is needed before these results can be used in clinical practice, but believe these markers could be used in the future to predict future brain health in older people with no signs of cognitive decline.