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Inflammation May Spur the Development of Alzheimer’s Disease

About 25 percent of people carry a gene that increases the risk of developing Alzheimer’s disease in old age. But not everyone who carries the gene, called APOE-E4, goes on to develop Alzheimer’s.

Scientists aren’t sure why, but a new study suggests that body-wide inflammation, which can arise because of heart disease, diabetes, infections or other conditions, may play a role.

The study found that APOE-E4 carriers who had persistent low-grade levels of inflammation were more likely to develop Alzheimer’s disease, and to show symptoms at a younger age, than those who did not suffer from inflammation.

“It is possible that chronic inflammation interacts with genetic vulnerability to increase the risk for Alzheimer’s disease,” said Dr. Wendy Qiu, a professor at Boston University School of Medicine who was a study author. “Since many elders have chronic low-grade inflammation after suffering from common diseases like cardiovascular diseases, diabetes, pneumonia and urinary tract infection, or after having surgeries, rigorously treating chronic systemic inflammation in APOE-E4 carriers could be effective for prevention of Alzheimer’s dementia.”

Whether treating the chronic inflammation with anti-inflammatory drugs could help to slow the onset of Alzheimer’s in those who are genetically predisposed to developing the disease remains unknown. Large studies addressing this specific question will be needed to determine whether such treatment is effective.

For the current study, published in the journal JAMA Network Open, the researchers looked at 2,656 men and women who were part of the large and ongoing Framingham Heart Study. They ranged in age from their 40s into their 80s, with a mean age at the start of the study of nearly 62.

The researchers determined their APOE gene status, including those who carried the APOE-E4 version of the gene that increases Alzheimer’s risk.

They also had ongoing measures of the participants’ levels of C-reactive protein, or CRP, a measure of general inflammation in the blood. CRP measures of 8 milligrams/liter of blood were considered high, and repeatedly high measure were an indication that someone suffered from chronic inflammation.

Over 17 years of follow-up, 194 of the study participants (7.3 percent) were diagnosed with Alzheimer’s disease or another form of dementia.

The researchers found that those people who had chronic inflammation and who carried the APOE-E4 gene were significantly more likely to be diagnosed with Alzheimer’s disease. The link was especially strong in those who had chronic inflammation but did not also have heart disease. Those with inflammation and other forms of the APOE gene were not at increased risk of developing Alzheimer’s.

APOE-E4 carriers with chronic inflammation were also more likely to begin showing symptoms of Alzheimer’s at a younger age than those who did not have inflammation.

Some of the study participants also underwent brain scans. The researchers found that APOE-E4 carriers with inflammation tended to have deterioration in parts of the brain affected by Alzheimer’s.

The findings add to a growing body of evidence that inflammation plays a role in Alzheimer’s disease. Other studies have shown, for example, that those with periodontal disease, an inflammatory condition, tended to have higher levels in the brain of beta-amyloid, a toxic component that builds up in the brains of those with Alzheimer’s and leads to amyloid plaques.

Scientists aren’t sure how inflammation may promote the development of Alzheimer’s. It is possible that chronic inflammation somehow damages brain cells, or neurons, priming them for the subsequent damage that occurs with the disease. But more research is needed to determine how inflammation might affect Alzheimer’s onset, and whether anti-inflammatory treatments may be beneficial.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Qiushan Tao, MD; Ting Fang Alvin Ang, MD; Charles DeCarli, MD; et al: “Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers.” JAMA Network Open, Oct. 19, 2018

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