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, Jaeil Shin

Research output: Contribution to journalArticle

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Abstract

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
Volume54
Issue number9
DOIs
Publication statusPublished - 2017 Nov 1

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Brain-Derived Neurotrophic Factor
Meta-Analysis
Alzheimer Disease
Cognitive Dysfunction
PubMed
Biomarkers

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Kim, Bo Yi ; Lee, Seon Heui ; Graham, Petra L. ; Angelucci, Francesco ; Lucia, Alejandro ; Pareja-Galeano, Helios ; Leyhe, Thomas ; Turana, Yuda ; Lee, I. Re ; Yoon, Ji Hye ; Shin, Jaeil. / Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment : a Comprehensive Systematic Review and Meta-analysis. In: Molecular Neurobiology. 2017 ; Vol. 54, No. 9. pp. 7297-7311.
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abstract = "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.",
author = "Kim, {Bo Yi} and Lee, {Seon Heui} and Graham, {Petra L.} and Francesco Angelucci and Alejandro Lucia and Helios Pareja-Galeano and Thomas Leyhe and Yuda Turana and Lee, {I. Re} and Yoon, {Ji Hye} and Jaeil Shin",
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Kim, BY, Lee, SH, Graham, PL, Angelucci, F, Lucia, A, Pareja-Galeano, H, Leyhe, T, Turana, Y, Lee, IR, Yoon, JH & Shin, J 2017, 'Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment: a Comprehensive Systematic Review and Meta-analysis', Molecular Neurobiology, vol. 54, no. 9, pp. 7297-7311. https://doi.org/10.1007/s12035-016-0192-9

Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment : a Comprehensive Systematic Review and Meta-analysis. / Kim, Bo Yi; Lee, Seon Heui; Graham, Petra L.; Angelucci, Francesco; Lucia, Alejandro; Pareja-Galeano, Helios; Leyhe, Thomas; Turana, Yuda; Lee, I. Re; Yoon, Ji Hye; Shin, Jaeil.

In: Molecular Neurobiology, Vol. 54, No. 9, 01.11.2017, p. 7297-7311.

Research output: Contribution to journalArticle

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T1 - Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer’s Disease and Mild Cognitive Impairment

T2 - a Comprehensive Systematic Review and Meta-analysis

AU - Kim, Bo Yi

AU - Lee, Seon Heui

AU - Graham, Petra L.

AU - Angelucci, Francesco

AU - Lucia, Alejandro

AU - Pareja-Galeano, Helios

AU - Leyhe, Thomas

AU - Turana, Yuda

AU - Lee, I. Re

AU - Yoon, Ji Hye

AU - Shin, Jaeil

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N2 - 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.

AB - 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.

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