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Serum Brain-Derived Neurotrophic Factor Across the Human Lifespan: A Systematic Review and Meta-Analysis
Wang, Z. X.; Li, X.; Dingsdale, H.. medRxiv (preprint), 2026-09-14
Topic: Brain proteins, microglia and lab models
BackgroundBone 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. MethodsWe 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 Pearsons r and synthesized using a three-level random-effects meta-analysis, with subgroup analyses by age, heterogeneity, and quality. FindingsSerum BDNF showed an age-specific decline. Among older adults ([≥]60 years), age was negatively associated with serum BDNF (pooled Fishers z=-0.139, 95% CI -0.166 to -0.111; p < 0.0001; I{superscript 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{superscript 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{superscript 2} = 64.4%; Q (16) = 87.25, p < 0.0001). InterpretationThough 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 BDNFs relation to cognitive aging and neurodegenerative risk. FundingNo funding was received. RegistrationOpen Science Framework - osf.io/264cp
Key findings
- Among older adults ([≥]60 years), age was negatively associated with serum BDNF (pooled Fishers z=-0.139, 95% CI -0.166 to -0.111; p < 0.0001; I{superscript 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{superscript 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{superscript 2} = 64.4%; Q (16) = 87.25, p < 0.0001).
Why it matters
This meta-analysis found that blood levels of BDNF decline with age in people over 60, but not in younger adults. It does not test any treatment, so it cannot show whether changing BDNF levels would prevent or treat dementia.
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Study details
- Study designmeta-analysis
- Effect size0.16%; 87.2%; 64.4%
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 37 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for sample size and studied in people because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 35 of the 94 points we could judge it on, which is 37 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Hayley Dingsdale: h-index 9 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Virginia: institution h-index 1,118 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 35 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 35 of the 94 points we could judge it on is 37 out of 100. |
| Total | 37 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Wang, Z. X., Li, X., & Dingsdale, H. (2026). Serum Brain-Derived Neurotrophic Factor Across the Human Lifespan: A Systematic Review and Meta-Analysis. medRxiv (preprint). https://doi.org/10.64898/2026.09.13.26362873
Vancouver
Wang ZX, Li X, Dingsdale H. Serum Brain-Derived Neurotrophic Factor Across the Human Lifespan: A Systematic Review and Meta-Analysis. medRxiv (preprint). 2026. doi:10.64898/2026.09.13.26362873.
BibTeX
@article{wang2026-94ee023c,
author = {Wang, Z. X. and Li, X. and Dingsdale, H.},
title = {{Serum Brain-Derived Neurotrophic Factor Across the Human Lifespan: A Systematic Review and Meta-Analysis}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.13.26362873},
url = {https://doi.org/10.64898/2026.09.13.26362873}
}
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