Inflammatory Proteins may Indicate a Lower Risk of Cognitive Decline in Alzheimer’s

January 16, 2023

Summary: Higher inflammation is associated with increased risk of dementia and Alzheimer’s disease. However, new studies show that a high level of certain inflammatory markers may suggest a lesser chance of cognitive decline in Alzheimer’s. In the study, researchers enrolled adults with proven amyloid beta deposits but with more or less normal cognition. The researchers found that these individuals had elevated cytokine, IL-12, and IFN-γ.

Alzheimer’s disease is among the leading causes of disability and mortality in the western world. However, what is worrisome is that despite more than a century of extensive research, science knows too little about it.

Just think there is no reliable test for diagnosing Alzheimer’s in its early stages. Even worse, no tests can reliably help predict the course of the disease.

Of course, science knows that there is an accumulation of amyloid and tau proteins, resulting in brain cell death in the condition. However, the role of the accumulation of these proteins in the disease is far from clear. For example, not all people who have amyloid accumulation in the brain may develop Alzheimer’s. It means that there is much to be understood yet.

Many studies suggest that low systemic inflammation may increase Alzheimer’s risk. However, a new study indicates that certain inflammatory markers may be related to a lower risk of cognitive decline in Alzheimer’s. It means that not all inflammatory responses indicate a higher Alzheimer’s risk.

There is an explanation for these contradicting findings. Inflammation is a very complex process; hundreds of proteins are involved in inflammatory processes. Therefore, uncontrolled and prolonged inflammation may increase the risk of chronic ailments. Nonetheless, it is also a defensive reaction.

Scientists have been trying hard to find out the etiology of Alzheimer’s disease. There are other reasons why researchers think that inflammation causes Alzheimer’s. Studies have identified many genes like CD33 and more related to higher Alzheimer’s (AD) risk. Most of these genes play an essential role in the immune system and inflammation.

Although inflammation may increase the risk of the condition, there is still much to be understood. Especially considering that inflammation also promotes healing, fights infections, and is an essential process in tissue regeneration.

For the study, researchers enrolled older adults who had undergone imaging tests. These were individuals known to have amyloid beta deposits in the brain, a protein associated with AD. Researchers wanted to understand why some people with amyloid in the brain progress to AD and others continue to live without cognitive decline.

The new study enrolled 298 participants aged 50 to 90 years. All of them had a normal cognitive functions, despite having amyloid deposits in the brain. Additionally, researchers tested their blood for nine cytokines to see the association between their level and cognitive decline.

To the researchers’ surprise, they found that those with high levels of a cytokine called interleukin-12 (IL-12) did not have any significant cognitive decline. However, cognitive decline was higher in those with lower IL-12 levels.

Similarly, they found that those with elevated levels of a cytokine called interferon-gamma (IFN-γ) were also less likely to experience cognitive decline.

Researchers think that they understand this phenomenon, though it may seem counterintuitive. Higher levels of these cytokines show that these individuals have better immunity against specific infectious agents. They are just better primed to fight specific infections.

These findings fit into the theory that early amyloid beta brain accumulation is a defensive response against infections. The immune system creates a sticky web to prevent infections from penetrating the brain. Unfortunately, in some people, this protective shield becomes the cause of irreversible damage to brain cells.

The latest findings suggest that those with higher IL-12 and IFN-γ levels might be able to control infections in their early stages and offer Alzheimer’s treatment.

Hence, researchers propose that monitoring IL-12 and IFN-γ levels in high-risk individuals may serve as a marker that may help predict the future. Especially considering that such a tool does not exist yet.

The Takeaway

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By Gurpreet Singh Padda, MD, MBA, MHP