Serum Brain-Derived Neurotrophic Factor Across the Human Lifespan: A Systematic Review and Meta-Analysis

Background: Bone marrow megakaryocytes, the primary source of brain-derived neurotrophic factor (BDNF) in the blood, secrete BDNF-packed platelets into the bloodstream. Reduced BDNF serum levels, a proxy for circulating blood-BDNF, have been linked to age-related neurological disorders, including dementia. Whether circulating BDNF levels decline with healthy aging or only in pathological contexts is unclear. Methods: We searched PubMed, Embase, Web of Science, and ScienceDirect up to September 2025 for human studies reporting associations between age and serum BDNF in non-clinical populations. Fifteen studies were included. Effect sizes were extracted or converted as Pearson's r and synthesized using a three-level random-effects meta-analysis, with subgroup analyses by age, heterogeneity, and quality. Findings: Serum BDNF showed an age-specific decline. Among older adults (>=60 years), age was negatively associated with serum BDNF (pooled Fisher's z=-0.139, 95% CI -0.166 to -0.111; p < 0.0001; I^2=0.16%). In younger adults (<60 years), the association was not significant (pooled z=-0.098, 95% CI -0.344 to 0.148; p=0.435; I^2 = 87.2%). Across all ages, serum BDNF was inversely associated with age (pooled z=-0.127, 95% CI -0.245 to -0.009; p = 0.035), though heterogeneity was substantial (I^2 = 64.4%; Q (16) = 87.25, p < 0.0001). Interpretation: Though not a feature of early or mid-adulthood, declining serum BDNF becomes pronounced in older age. This age-specific trajectory provides a reference point for future studies examining BDNF's relation to cognitive aging and neurodegenerative risk.