Circulating Brain-Derived Neurotrophic Factor and Indices of Metabolic and Cardiovascular Health: Data from the Baltimore Longitudinal Study of Aging

Abstract

BackgroundBesides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF) is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile.Methodology/Principal FindingsTo determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age ∼70), in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3), and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin.Conclusion/SignificancePlasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain) remains to be determined.

Impaired Adaptive Cellular Responses to Oxidative Stress and the Pathogenesis of Alzheimer's Disease

“…In some human studies BDNF levels in serum (188) or plasma (103) exhibited a negative correlation with age. An analysis of plasma BDNF levels in 496 middle-aged and elderly subjects from the Baltimore Longitudinal Study of Aging demonstrated a negative correlation between plasma BDNF levels and age in both males and females (56). The latter study further demonstrated that plasma BDNF levels are positively associated with risk factors for metabolic syndrome and cardiovascular disease, independently of age.…”

Brain derived neurotrophic factor (BDNF) in cardiometabolic physiology and diseases

“…It was reported that leptin shows its neuroprotective effect in the brain by increasing the level of BDNF (50). In humans, plasma BDNF level inversely correlated to adiponectin level only in male gender, but it was correlated with the components of metabolic syndrome in both sexes (16). However, it is possible that such observations may be resultant from reactive mechanisms rather than direct etiological relations, and the interactions among the neurotrophins and other adipokines need to be explored further.…”

“…Circulating BDNF was reported to correlate positively to LDL cholesterol, total cholesterol and triglyceride levels in humans (16,17). In animal experiments, BDNF treatment reported to lower blood glucose, non-esterified free fatty acid, total cholesterol and phospholipid levels significantly in diabetic models, along with liver weight, liver triglyceride contents and fatty liver in histological examinations (28).…”

“…Circulating but not the platelet level of BDNF correlated negatively with age, body mass index (BMI) and total cholesterol, whereas no difference with respect to gender was detected by the same investigators. In a study in which the subjects were screened for long years starting from a healthy period, circulating BDNF level was higher in women and it decreased with advancing age in both genders (16). Moreover, blood level of BDNF had a positive correlation with diastolic blood pressure, total cholesterol, lowdensity lipoprotein cholesterol, adipose tissue mass, body mass index, diastolic blood pressure and triglyceride, showing some differences between men and women (16,17).…”

“…In a study in which the subjects were screened for long years starting from a healthy period, circulating BDNF level was higher in women and it decreased with advancing age in both genders (16). Moreover, blood level of BDNF had a positive correlation with diastolic blood pressure, total cholesterol, lowdensity lipoprotein cholesterol, adipose tissue mass, body mass index, diastolic blood pressure and triglyceride, showing some differences between men and women (16,17). Importantly, women with low plasma BDNF had greater all-cause mortality risk than women with high plasma BDNF in a study conducted in old age individuals (18).…”