Peripheral brain-derived neurotrophic factor levels in Alzheimer's disease and mild cognitive impairment

a comprehensive systematic review and meta-analysis

Bo Yi Kim, Seon Heui Lee, Petra L. Graham, Francesco Angelucci, Alejandro Lucia, Helios Pareja-Galeano, Thomas Leyhe, Yuda Turana, I. Re Lee, Ji Hye Yoon, Jae Il Shin*

*Corresponding author for this work

    Research output: Contribution to journalReview article

    9 Citations (Scopus)


    Alzheimer's disease (AD) is becoming a growing global problem, and there is an urgent need to identify reliable blood biomarkers of the risk and progression of this condition. A potential candidate is the brain-derived neurotrophic factor (BDNF), which modulates major trophic effects in the brain. However, findings are apparently inconsistent regarding peripheral blood BDNF levels in AD patients vs. healthy people. We thus performed a systematic review and meta-analysis of the studies that have examined peripheral BDNF levels in patients with AD or mild cognitive impairment (MCI) and healthy controls. We searched articles through PubMed, EMBASE, and hand searching. Over a total pool of 2061 potential articles, 26 met all inclusion criteria (including a total of 1584 AD patients, 556 MCI patients, and 1294 controls). A meta-analysis of BDNF levels between early AD and controls showed statistically significantly higher levels (SMD [95 % CI]: 0.72 [0.31, 1.13]) with no heterogeneity. AD patients with a low (<20) mini-mental state examination (MMSE) score had lower peripheral BDNF levels compared with controls (SMD [95 % CI]: -0.33 [-0.60, -0.05]). However, we found no statistically significant difference in blood (serum/plasma) BDNF levels between all AD patients and controls (standard mean difference, SMD [95 % CI]: -0.16 [-0.4, 0.07]), and there was heterogeneity among studies (P <0.0001, I (2) = 85.8 %). There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age, sex, and drug use. In conclusion, this meta-analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents. At present, however, this could not be concluded from individual studies.

    Original languageEnglish
    Pages (from-to)7297-7311
    Number of pages15
    JournalMolecular Neurobiology
    Issue number9
    Publication statusPublished - Nov 2017


    • Alzheimer’s disease
    • Mild cognitive impairment
    • BDNF
    • Biomarkers

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