Low brain‐derived neurotrophic factor (BDNF) levels in serum of Huntington's disease patients

Abstract

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive degeneration of neurons in basal ganglia and in brain cortex. Brain-derived neurotrophic factor (BDNF) is a pro-survival factor for striatal neurons. Some evidence implicates a brain BDNF deficiency, related to mutated huntingtin expression, in the selective vulnerability of striatal neurons in HD. We compared BDNF serum levels in 42 patients with HD (range 28-72 years, mean age 51.9 +/- 11.5), and 42 age-matched healthy subjects (range 25-68 years, mean age 48.2 +/- 12.5). We evaluated the potential relationship between BDNF serum levels, CAG repeat number (range 40-54, mean 44.8 +/- 3.4) and duration of illness (range 6-228 months, mean 103.6 +/- 62.1). Serum BDNF levels were significantly lower in patients than in age-matched healthy subjects. Lower BDNF levels were associated with a longer CAG repeat length and a longer duration of illness. Severity of the illness, as assessed by the Unified Huntington's Disease Rating Scale (UHDRS) motor and cognitive scores, was negatively related to serum BDNF levels. These results in vivo confirm that the huntingtin mutation causes BDNF production to decline and show that the BDNF deficiency is detectable in HD patients' sera. Further studies on a larger sample size should confirm whether BDNF concentrations in patients' serum could be a useful clinical marker related to the patients' disease phenotype.

First use of creatine hydrochloride in premanifest Huntington disease

“…This delayed increase coincides with significant improvements in memory and learning achieved after longitudinal intervention. Our results are in accord with previous evidence demonstrating reduced BDNF/BDNF levels in Huntington's disease, in both humans and animal models [95][96][97][98][99][100] , and activity-dependent increases in BDNF expression in animals 77,82,104,105,109,110 and in human populations [106][107][108] . During the course of this investigation, however, a recent publication has questioned the utility of BDNF measurement as a biomarker for the monitoring of Huntington's disease 162 .…”

“…Consistent with previous reports [95][96][97][98][99][100][101] , the ELISA results indicated lower levels of BDNF in the whole blood of Huntington's disease individuals, relative to normative data ( Figure 26). The assay to detect changes in mean BDNF concentration over the time period of the study revealed a non-significant reduction in mean BDNF levels after the control period (p=0.838) which worsened after one round of intervention (p=0.393).…”

“…BDNF is expressed within the hypothalamus 88 , where it is associated with satiety/appetite 89,90 , and also in the hippocampus, from where the BDNF protein is transported to the striatum and promotes survival of striatal neurons [91][92][93][94][95] . Reduced BDNF levels are associated with…”

“…Huntington's disease [95][96][97][98][99][100][101] and are suspected of contributing to striatal pathology 93,94,[100][101][102] .…”

Cerebrospinal Fluid Biomarkers for Huntington’s Disease

“…In most cases the overwhelming mass of the peripheral tissues inevitably dwarfs the contribution of substances that are released from dying neurons and can penetrate the blood-brain barrier, especially given the very slow rate of CNS cell death in HD. Even seemingly 'CNS-specific' entities that can be detected in peripheral blood, such as brain-derived neurotrophic factor (BDNF) [17], may have peripheral sources that confound their interpretation [18].…”