Peripheral Brain-Derived Neurotrophic Factor Levels in Alzheimer's Disease and Mild Cognitive Impairment: a Comprehensive Systematic Review and Meta-analysis.
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, I2= 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.
College of Medicine, Ewha Womans University, Seoul, South Korea.
Bo Yi
BY
Kim
Department of Nursing Science, College of Nursing, Gachon University, Incheon, South Korea.
Seon Heui
SH
Lee
Department of Statistics, Macquarie University, Sydney, Australia.
Petra L
PL
Graham
Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
Francesco
F
Angelucci
Research Institute of Hospital 12 de Octubre (i+12), European University of Madrid, Madrid, Spain.
Alejandro
A
Lucia
Research Institute of Hospital 12 de Octubre (i+12), European University of Madrid, Madrid, Spain.
Helios
H
Pareja-Galeano
Center of Old Age Psychiatry, Psychiatric University Hospital, Basel, Switzerland.
Thomas
T
Leyhe
Department of Neurology, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.
Yuda
Y
Turana
Department of Pediatrics, Yonsei University College of Medicine, 50 Yonsei-Ro, Seoul, 120-752, Republic of Korea.
I Re
IR
Lee
College of Medicine, Ewha Womans University, Seoul, South Korea.
Ji Hye
JH
Yoon
Department of Pediatrics, Yonsei University College of Medicine, 50 Yonsei-Ro, Seoul, 120-752, Republic of Korea. shinji@yuhs.ac.
Jae Il
JI
Shin
D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D060825:Cognitive Dysfunction / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D006801:Humans
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
Alzheimer’s disease; BDNF; Biomarkers; Mild cognitive impairment