Alzheimer’s Disease Linked To Chronic Inflammation Leading To New Treatments

3D medical background with magnifying glass examining brain depicting alzheimers research

It is already understood that possessing the ApoE4 gene is the major genetic risk factor of Alzheimer’s disease (AD). What has been unknown is why not all ApoE4 carriers develop AD. Boston University School of Medicine (BUSM) researchers have done the work to deliver us an answer. By using data collected from an over three decades long study (from August 13, 1971-November 27, 2017), they discovered that chronic systemic inflammation may make the brain more vulnerable to AD in ApoE4 carriers.

“Finding out what mediating factors for ApoE4 increase AD risk is important for developing intervention and prevention of the disease,” explained corresponding author Wendy Qiu, MD, PhD, associate professor of psychiatry and pharmacology & experimental therapeutics at BUSM. “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 ApoE4 carriers could be effective for prevention of Alzheimer’s dementia.”

In the Framingham heart study, the researchers studied around 3,000 human subjects with the ApoE4 gene. It was a cohort with long and intensive follow-up that includes multiple measurements of serum CRP taken during a 2-decade period. C-reactive protein (CRP) is an immune system response to toxins or injuries in systemic inflammation. In other words, C-reactive protein is a biomarker of low-grade inflammation. They analyzed those with and without chronic low-grade inflammation defined by sequential C-reactive protein measurements.

This study was monitored by a National Heart, Lung, and Blood Institute Observational Study Monitoring Board and followed their guidelines. The results were published in the journal JAMA Network Open.

Cynthia Lemere, a scientist at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, a Harvard Medical School professor, and also chairwoman of the Alzheimer’s Association’s Medical and Scientific Advisory Council said in an e-mail to Boston Globe that the study appeared to be rigorous and offered “a new and important piece of information… This study adds to the growing evidence that inflammation plays a role in Alzheimer’s disease… These results provide support for the role of peripheral, chronic inflammation in AD, and suggest that early treatment with anti-inflammatory therapies may be helpful in staving off AD, at least in ApoE4 carriers.”

In conclusion, anti-inflammatory treatments could be effective for AD prevention. This can be detected with a common clinical test which can be done routinely. One method could be to conduct a clinical follow-up and treatment of high levels of C-reactive protein by sequential measurements of C-reactive protein. Qiu believes that without chronic low-grade inflammation there would be no difference of Alzheimer’s risk between ApoE4 and non-ApoE4 carriers.