Peripheral Blood Brain-Derived Neurotrophic Factor as a Biomarker of Alzheimer’s Disease: Are There Methodological Biases?

Abstract

Mounting evidence that alterations in brain-derived neurotrophic factor (BDNF) levels and signaling may be involved in the etiopathogenesis of Alzheimer’s disease (AD) has suggested that its blood levels could be used as a biomarker of the disease. However, higher, lower, or unchanged circulating BDNF levels have all been described in AD patients compared to healthy controls. Although the reasons for such different findings are unclear, methodological issues are likely to be involved. The heterogeneity of participant recruitment criteria and the lack of control of variables that influence circulating BDNF levels regardless of dementia (depressive symptoms, medications, lifestyle, lack of overlap between serum and plasma, and experimental aspects) are likely to bias result and prevent study comparability. The present work reviews a broad panel of factors, whose close control could help reduce the inconsistency of study findings, and offers practical advice on their management. Research directed at elucidating the weight of each of these variables and at standardizing analytical methodologies is urgently needed.

Effect of 9 weeks continuous vs. interval aerobic training on plasma BDNF levels, aerobic fitness, cognitive capacity and quality of life among seniors with mild to moderate Alzheimer’s disease: a randomized controlled trial

“…Thus, our method based on global recommendations aiming to improve and maintain health in older adults may not have been sufficiently intense in some participant to induce a significant effect on plasma BDNF production [24,28,61]. Several additional factors can however influence the basal synthesis of BDNF at the individual level such as genetic variation, metabolic disorders, and/or inflammatory process and hence the BDNF response to aerobictype training [62]. For example, some authors consider AD as a metabolic disorder mediated by insulin-resistance at the brain level [63].…”

Effect of social isolation stress on saliva BDNF in rat

“…The relative abundance of various substances in saliva may reflect their abundance in the brain more precisely than is the case for those measured in blood [40,41]. Blood BDNF passes from the brain through the blood-brain barrier, and therefore alterations in blood the BDNF level may be associated with disease pathology [42]. A previous study has indicated that the level of BDNF in the brain is correlated with its expression in the salivary gland via the blood [3].…”

The Effect of Mindfulness-Based Intervention on Brain-Derived Neurotrophic Factor (BDNF): A Systematic Review and Meta-Analysis of Controlled Trials

“…Previous studies show peripheral BDNF is related to numerous brain disorders. A recent meta-analysis finds that lower levels of peripheral BDNF are associated with an increased risk of depression (Brunoni et al, 2008 ), Alzheimer's disease (Balietti et al, 2018 ), Parkinson's disease (Rahmani et al, 2019 ), and strokes with an unfavorable outcome (Xu et al, 2018 ). There have been attempts to provide external BDNF, but this has not been successful (Houlton et al, 2019 ) due to poor blood–brain barrier permeability and short therapeutic half-life (Poduslo and Curran, 1996 ).…”