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Chronic inflammation may increase Alzheimer's risk for APOE4 carriers



Peripheral chronic inflammation was associated overall with increased risks of Alzheimer's disease and earlier onset of disease in apolipoprotein E4 ( APOE4 ) gene carriers, researchers reported.

Defined as C-reactive protein (CRP) at concentrations of 8, 9, or 10 mg / L, this low-grade inflammation was only seen in individuals carrying APOE4 especially in cardiovascular disease (HR 6, 63, 95% CI 1.80-24.50, P = 0.005), according to Wendy Qiu, MD, PhD, from the Boston University School of Medicine and colleagues.

In addition, APOE4 carriers with chronic inflammation had an increased risk of a previous outbreak as APOE4 carriers who had no inflammation (HR 3.52, 95% CI 1

.27 -9.75, P = 0.009), they reported in JAMA Network Open .

"Finding out what factors for APOE4 increase in Alzheimer's disease is important for the development of interventions and disease prevention," Qiu said in a statement. "Since many older people have chronic lung infections after suffering from common diseases such as cardiovascular disease, diabetes, pneumonia and urinary tract infections, or after surgical procedures, rigorous treatment of chronic systemic inflammation in APOE4 carriers could be effective for the prevention of Alzheimer's dementia. "

The results are consistent with those from Alzheimer's animal models and recent human research, noted Keenan Walker, PhD, from the Baltimore Johns Hopkins School of Medicine, who was not involved in the study. 19659002] "It is becoming increasingly clear that inflammation is an important part of the pathophysiology of Alzheimer's disease," said Walker MedPage Today . "This study provides additional evidence that low-grade systemic inflammation can be a potent risk factor for the development of Alzheimer's disease."

In the study, Qius group evaluated data from 2,656 members of the Framingham Offspring Study (Generation 2). , a cohort of children from the Framingham Heart Study. They defined the chronic inflammatory status with at least two longitudinal serum CRP measurements above the given values.

The patients were on average about 61 years old in their last CRP measurement. During 17 years of follow-up, 194 individuals developed dementia, 152 of whom had Alzheimer's disease.

This phenomenon of increased Alzheimer's disease and the earlier onset of disease in APOE4 carriers was not observed in APOE3 and APOE2 carriers with chronic low-grade inflammation. Although APOE2 carriers had higher CRP levels with age than, for example, APOE3 and APOE4 carriers, high CRP levels were not associated with Alzheimer's risk

Brain atrophy was associated in the temporal lobe in a subgroup of subjects with magnetic resonance imaging of the brain (n = 1,761), APOE4 and chronic low-grade inflammation (beta = -0.88, SE 0.22, P <0.001) and hippocampus (beta = -0.04, SE 0.01, P = 0.005).

"Our results suggest that chronic low-grade inflammation interacts with APOE4 to accelerate the onset of Alzheimer's disease in a CRP-dependent pattern," Qiu and colleagues observed.

"Since it is well documented that infections and inflammation are common in older people, preclinical studies have reported that the inflammation induced Alzheimer's disease pathologically in mice that could only carry APOE4 Findings explain why APOE4 carriers have an increased risk for Alzheimer's in old age and suggest that the treatment of chronic mild inflammation may delay the onset of Alzheimer's disease in APOE4 carriers ", they concluded.

The study's limitations include the lack of more frequent CRP assessments, the limited sample size for sub-analyzes, and their inability as an observational study to prove causality. The Framingham cohort lacks ethnic diversity, and findings may not apply to non-white populations.

Funding for this study was provided by the National Heart, Lung and Blood Institute and the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. The researchers reported no conflicts of interest. 1969-12-31T19: 00: 00-0500

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