Background: Brain derived neurotrophic factor (BDNF) may play a central role in the pathogenesis
of Alzheimer's disease (AD) through neurotrophic effects on basal cholinergic neurons. Reduced
serum levels of BDND are observed among AD patients and may predict AD risk. Nevertheless, knowledge
about factors associated with its levels in blood is lacking.
Objective: To identify clinical and demographic correlates of serum BDNF levels.
Methods: BDNF was measured from serum collected between 1992-1996 and 1998-2001 in participants
from the Original and Offspring cohorts of the Framingham Study, respectively. A cross-sectional
analysis was done to evaluate the relationship between clinical measures and BDNF levels using standard
linear regression and stepwise models. Analyses were conducted in the total sample and separately
in each cohort, and were adjusted for age and sex.
Results: BDNF was measured in 3,689 participants (mean age 65 years, 56% women; 82% Offspring).
Cigarette smoking and high total cholesterol were associated with elevated BDNF levels, and history of
atrial fibrillation was associated with decreased levels. Elevated BDNF levels were related to greater
physical activity and lower Tumor Necrosis Factor-α levels in Offspring. Stepwise models also revealed
associations with statin use, alcohol consumption and Apolipoprotein Eε4 genotype.
Conclusion: Serum BDNF correlates with various metabolic, inflammatory and life-style measures
which in turn have been linked with risk of AD. Future studies of serum BDNF should adjust for these
correlates and are needed to further explore the underlying interplay between BDNF and other factors in
the pathophysiology of cognitive impairment and AD.