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Peripheral chronic inflammation was associated with increased risk of Alzheimer's disease in general and earlier onset of disease in apolipoprotein E4 (APOE4) gene carriers, report the researchers.
Defined as a C-reactive protein (CRP) of 8, 9 or 10 mg / L, this low-grade inflammation was associated with an increased risk of Alzheimer's disease only in the carriers APOE4, especially in the absence of cardiovascular diseases (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 her colleagues.
In addition, APOE4 carriers with chronic inflammation had an increased risk of early onset of the disease compared with APOE4 carriers that did not have inflammation (HR 3.52, 95% CI: 1.27-9.75, P= 0.009), they reported in JAMA Network open now.
"Discover which mediation factors for APOE4 increase the risk of Alzheimer's disease is important to develop an intervention and prevention of the disease, "Qiu said in a statement, or after undergoing surgery, rigorously treat chronic systemic inflammation APOE4 carriers could be effective in preventing Alzheimer's dementia. "
The findings are consistent with those of animal models with Alzheimer's disease and recent research on humans, said Keenan Walker, PhD of the Johns Hopkins School of Medicine in Baltimore, who did not not participated in the study.
"It is becoming increasingly clear that inflammation is an important component of the pathophysiology of Alzheimer's disease," Walker said. MedPage today. "This study provides additional evidence that low-grade systemic inflammation may be a potent risk factor for the development of Alzheimer's disease."
In the study, Qiu's 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 chronic inflammatory status as having at least two longitudinal serum CRP measurements greater than the pre-specified levels.
Patients averaged about 61 years of age on their last CRP test. During the 17 years of follow-up, 194 people developed dementia, including 152 with Alzheimer's disease.
This phenomenon of increase of Alzheimer's disease and early onset of the disease at APOE4 carriers has not been observed in APOE3 and APOE2 carriers with chronic inflammation of low grade. Even if APOE2 carriers had higher CRP levels with age APOE3 and APOE4 carriers, for example, high CRP levels were not related to the risk of Alzheimer's in this group.
In a subgroup of study participants who had magnetic resonance imaging of the brain (n = 1,761), APOE4 and low grade chronic inflammation was associated with temporal lobe cerebral atrophy (beta = -0.88, SE 0.22, P<0.001) and hippocampus (beta = -0.04, SE 0.01, P= 0.005).
"Our results suggest that low grade chronic inflammation interacts with APOE4 to accelerate the onset of Alzheimer's disease according to a scheme dependent on the CRP level, "observed Qiu and colleagues.
"As it is well established that infection and inflammation are common in the elderly, preclinical studies have shown that inflammation induces pathological features of Alzheimer's disease in patients with Alzheimer's disease. mice that only wore APOE4, our results may explain why APOE4 the carriers have an increased risk of Alzheimer's disease in old age and suggest that the treatment of low grade chronic inflammation could delay the onset of Alzheimer's disease in APOE4 carriers, "they concluded.
The limitations of the study include its lack of more frequent assessments of CRP, the limited sample size for sub-analyzes, and its inability, as observational research, to prove causality. The Framingham cohort lacks ethnic diversity and the results may not be applicable to non-white populations.
Funding for this study was provided by the National Institute of the Heart, Lung and Blood and by grants from the National Institute of Neurological Disorders and Stroke and the National Institute aging. The researchers have not reported any conflicts of interest.
1969-12-31T19: 00: 00-0500
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