Brain-Derived Neurotrophic Factor Mitigates the Association Between Platelet Dysfunction and Cognitive Impairment

Bélanger, Jean-Christophe; Bouchard, Véronique; Blanc, Jessica Le; Starnino, Louisia; Welman, Mélanie; Chabot-Blanchet, Malorie; Busseuil, David; Chertkow, Howard; DʼAntono, Bianca; Lordkipanidzé, Marie

doi:10.3389/fcvm.2021.739045

Cited by 15 publications

(12 citation statements)

References 45 publications

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“… 65 This neurotrophin is abundant in platelets, 65 and its serum concentration correlates positively with soluble P-selectin that may be considered a marker of platelet activation. 66 The role of GDNF in the growth and maintenance of the central and peripheral nervous systems is also well described. 67 However, it is also expressed in peripheral tissues, including digestive, respiratory, hematopoietic and urogenital systems, heart, blood, muscles and skin.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Adverse Outcomes in Healthy Aging Adults: Coronary Artery Disease, Lower Educational Status and Higher P-Selectin Levels

Batko-Szwaczka¹,

Francuz²,

Kosowska³

et al. 2022

CIA

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Background Societal aging – as a global demographic phenomenon – shows no indication of abating. As a result, the problem of age-associated disability and related long-term care is emerging as a major public health challenge. It is important that methods for identifying older adults at risk of adverse outcomes are implemented early. Methods The study group consisted of 145 individuals, 44.1% women, who were randomized from community-dwelling 60–74-year-old adults. A comprehensive geriatric assessment was supplemented with Fried frailty phenotype evaluation and blood tests (including adhesion molecules, matrix metalloproteinases and neurotrophic factors). A follow-up by phone call was made for at least 3 years after the initial examination. Composite endpoint (CE) included falls, hospitalization, institutionalization and death. Results Mean study group age was 66.5 ± 4.1 years ( ) and mean number of diseases was 3.7 ± 2.2. Functional status of the subjects was good, as indicated by high Barthel Index scores of 99.1 ± 2.4, MMSE scores of 29.0 ±1.5 and no frailty case. During a three-year follow-up, 71 participants (49.0%) experienced any CE-events. The Wilcoxon-Gehan test indicates that a higher probability of three-year CE completion was associated with an age >65 years (P = 0.006), coronary artery disease (CAD) (P = 0.008), 6-Minute Walk Test <432 m (P = 0.034), serum glucose >120 mg/dL (P = 0.047), serum cortisol >10 μg/dL (P = 0.011), leptin ≥15 ng/mL (P = 0.018), P-selectin ≥23 ng/mL (P = 0.006) and GDNF ≥20 pg/mL (P = 0.004). CAD (OR = 3.64, 95% CI = 1.53−8.69, P = 0.004), educational status (OR = 0.87, 95% CI = 0.77−0.98, P = 0.022) and P-selectin levels (OR = 1.07, 95% CI = 1.02−1.13, P = 0.013) were independent measures predicting three-year CE occurrence in multivariate logistic regression analysis adjusted for clinical and functional measures, and blood tests. Conclusion Coronary artery disease, poorer lower educational status and higher P-selectin levels were predictive of adverse outcomes in the community-dwelling healthy-aging early-old adults during three-year follow-up.

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Section: Discussionmentioning

confidence: 99%

Predictors of Adverse Outcomes in Healthy Aging Adults: Coronary Artery Disease, Lower Educational Status and Higher P-Selectin Levels

Batko-Szwaczka¹,

Francuz²,

Kosowska³

et al. 2022

CIA

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“…Between September 2012 and June 2017, 1,280 older men and women [ n = 673 with coronary artery disease (CAD) and n = 607 without CAD], were recruited from the André and France Desmarais Hospital Cohort of the Montreal Heart Institute into the BEL-AGE study that seeks to examine the role of psychological burden on pathological aging, as previously described ( Gentile et al, 2019 ; Belanger et al, 2021 ; Vaillancourt et al, 2021 ). To do so, the BEL-AGE study follows these 1,280 individuals in time and records information regarding aging and psychological condition, and screens for mild cognitive dysfunction.…”

Section: Methodsmentioning

confidence: 99%

“…Participants with disorders that did not affect their ability to provide informed consent, such as anxiety and depressive disorders, were not excluded ( Vaillancourt et al, 2021 ). The criteria defining the CAD and non-CAD status were described earlier ( Belanger et al, 2021 ). The CAD status was self-reported and confirmed by medical record review.…”

Section: Methodsmentioning

confidence: 99%

Clinical Correlates Identify ProBDNF and Thrombo-Inflammatory Markers as Key Predictors of Circulating p75NTR Extracellular Domain Levels in Older Adults

Fleury

Schnitzer

Ledoux-Hutchinson

et al. 2022

Front. Aging Neurosci.

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The p75NTR receptor binds all neurotrophins and is mostly known for its role in neuronal survival and apoptosis. Recently, the extracellular domain (ECD) of p75NTR has been reported in plasma, its levels being dysregulated in numerous neurological diseases. However, the factors associated with p75NTR ECD levels remain unknown. We investigated clinical correlates of plasma p75NTR ECD levels in older adults without clinically manifested neurological disorders. Circulating p75NTR levels were measured by enzyme-linked immunosorbent assay in plasma obtained from participants in the BEL-AGE cohort (n = 1,280). Determinants of plasma p75NTR ECD levels were explored using linear and non-linear statistical models. Plasma p75NTR ECD levels were higher in male participants; were positively correlated with circulating concentrations of pro-brain-derived neurotrophic factor, and inflammatory markers interleukin-6 and CD40 Ligand; and were negatively correlated with the platelet activation marker P-selectin. While most individuals had p75NTR levels ranging from 43 to 358 pg/ml, high p75NTR levels reaching up to 9,000 pg/ml were detectable in a subgroup representing 15% of the individuals studied. In this cohort of older adults without clinically manifested neurological disorders, there was no association between plasma p75NTR ECD levels and cognitive performance, as assessed by the Montreal Cognitive Assessment score. The physiological relevance of high p75NTR ECD levels in plasma warrants further investigation. Further research assessing the source of circulating p75NTR is needed for a deeper understanding of the direction of effect, and to investigate whether high p75NTR ECD levels are predictive biomarkers or consequences of neuropathology.

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“…(2) the timing of measurement (accounting for diurnal variations) (Begliuomini et al, 2008;Pluchino et al, 2009); (3) psychological/psychiatric disorders (Bocchio-Chiavetto et al, 2010;Leyhe et al, 2008;Polyakova et al, 2015;Ventriglia et al, 2013); (4) physical activity (Cho et al, 2012;Gomes et al, 2014;Slusher et al, 2018); ( 5) duration of the sample storage period (Bus et al, 2011;Naegelin et al, 2018;Trajkovska et al, 2007;Tsuchimine et al, 2014), and (6) role of platelet activation (Bélanger et al, 2021;Karege et al, 2005). Each of these factors can negatively influence the consistency of results.…”

Section: Measurement Of Bdnfmentioning

confidence: 99%

BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges

Thakkar

Acevedo

2023

Brain and Behavior

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Introduction:The primary objective of this paper is to (1) provide a summary of human studies that have used brain derived neurotrophic factor (BDNF) as a biomarker, (2) review animal studies that help to elucidate the mechanistic involvement of BDNF in the development and maintenance of neuropathic pain (NP), and (3) provide a critique of the existing measurement techniques to highlight the limitations of the methods utilized to quantify BDNF in different biofluids in the blood (i.e., serum and plasma) with the intention of presenting a case for the most reliable and valid technique. Lastly, this review also explores potential moderators that can influence the measurement of BDNF and provides recommendations to standardize its quantification to reduce the inconsistencies across studies. Methods:In this manuscript we examined the literature on BDNF, focusing on its role as a biomarker, its mechanism of action in NP, and critically analyzed its measurement in serum and plasma to identify factors that contribute to the discrepancy in results between plasma and serum BDNF values.Results: A large heterogenous literature was reviewed that detailed BDNF's utility as a potential biomarker in healthy volunteers, patients with chronic pain, and patients with neuropsychiatric disorders but demonstrated inconsistent findings. The literature provides insight into the mechanism of action of BDNF at different levels of the central nervous system using animal studies. We identified multiple factors that influence the measurement of BDNF in serum and plasma and based on current evidence, we recommend assessing serum BDNF levels to quantify peripheral BDNF as they are more stable and sensitive to changes than plasma BDNF. Conclusion:Although mechanistic studies clearly explain the role of BDNF, results from human studies are inconsistent. More studies are needed to evaluate the methodological challenges in using serum BDNF as a biomarker in NP.

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Brain-Derived Neurotrophic Factor Mitigates the Association Between Platelet Dysfunction and Cognitive Impairment

Cited by 15 publications

References 45 publications

Predictors of Adverse Outcomes in Healthy Aging Adults: Coronary Artery Disease, Lower Educational Status and Higher P-Selectin Levels

Predictors of Adverse Outcomes in Healthy Aging Adults: Coronary Artery Disease, Lower Educational Status and Higher P-Selectin Levels

Clinical Correlates Identify ProBDNF and Thrombo-Inflammatory Markers as Key Predictors of Circulating p75NTR Extracellular Domain Levels in Older Adults

BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges

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