Serum Brain-Derived Neurotrophic Factor Across the Human Lifespan: A Systematic Review and Meta-Analysis
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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; I²=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; I² = 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 (I² = 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.
Funding
No funding was received.
Registration
Open Science Framework - osf.io/264cp
