Lower brain-derived neurotrophic factor levels are associated with age-related memory impairment in community-dwelling older adults: the Sefuri study

Abstract

The beneficial effects of brain-derived neurotrophic factor (BDNF)—a member of the neurotrophin family—on cognitive function or dementia are well established in both rodents and human beings. In contrast, little is known about the association of proBDNF—a precursor protein with opposing neuronal effects of BDNF—with cognitive function in non-demented older adults. We analyzed brain magnetic resonance imaging findings of 256 community-dwelling older adults (mean age of 68.4 years). Serum BDNF and proBDNF levels were measured by quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that older age, less physical activity, hippocampal atrophy, and lower BDNF levels were independently associated with memory impairment determined by the Rivermead Behavioral Memory Test. Path analysis based on structural equation modeling indicated that age, sport activity, hippocampal atrophy and BDNF but not proBDNF were individually associated with Rivermead Behavioral Memory Test scores. These findings suggest that impaired BDNF function, in addition to physical inactivity and hippocampal atrophy, is associated with age-related memory impairment. Therefore, BDNF may be a potential target for dementia prevention.

ProBDNF induces sustained elevation of intracellular Ca2+ possibly mediated by TRPM7 channels in rodent microglial cells

“…Indeed, proBDNF is shown to promote a pruning of spines through the p75NTR‐RhoA signaling, while mature BDNF induces maturation of spines through the stimulation of TrkB‐Rac1 signaling (Orefice, Shih, Xu, Waterhouse, & Xu, 2016). These reports suggest that proBDNF and mature BDNF elicit opposing neuronal responses in the brain (Greenberg et al, 2009; Mizoguchi, Oyama, Imamura, Node, & Monji, 2019; Mizoguchi, Yao, Imamura, Hashimoto, & Monji, 2020; Yang et al, 2014).…”

No association of both serum pro‐brain‐derived neurotrophic factor (proBDNF) and BDNF concentrations with depressive state in community‐dwelling elderly people

“…In addition, a positive correlation was found between mild depression and overall serum BDNF levels. However, the authors reported a synergistic correlation between low region and hippocampal atrophy in the analysis of each serum BDNF tertile 33 …”

“…The results of the present study may indicate a negative association between serum BDNF and LMII‐DR. In a report by Mizoguchi et al ., the serum Log 10 BDNF of dementia‐free individuals was negatively correlated with the Rivermead Behavioural Memory Test 33 . However, that study involved only a small number of participants, so the serum BDNF levels may have been distorted.…”

“…However, in the present study, serum proBDNF was not associated with LMII‐DR or depressive state, probably because proBDNF is associated with major depression and may not respond at the level of depressive state. In a report by Mizoguchi et al ., proBDNF was not directly related to memory dysfunction in the elderly living in the community 33 . The authors suggested that a newly identified BDNF pro‐peptide as one of the possibilities.…”

“…The concentrations of serum BDNF and proBDNF are expressed as ng/mL. Measurements were performed according to the manufacturer's instructions and based on our experience, as previously reported 20,33 …”