The molar ratio between PAI‐1 and BDNF is increased in Alzheimer’s disease patients with full dementia and negatively correlates with MMSE score

Abstract

AbstractBackgroundIn a previous study, we demonstrated that the enzyme plasminogen activator inhibitor‐1 (PAI‐1), which inhibits plasmin synthesis in the central nervous system (CNS), is increased in the serum of patients with Alzheimer’s disease (AD). In addition to reducing the accumulation of Ab, plasmin in the CNS regulates the synthesis of the trophic factor brain‐derived neurotrophic factor (BDNF) which appears to be altered in the brain of patients with AD. We investigated whether BDNF serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI‐1/BDNF ratio in these patient groups and correlated with cognitive scores as measured by Mini‐Mental State Examination (MMSE).Method40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and BDNF serum concentration were quantified by sandwich ELISAs. Comparisons among the experimental groups (AD dementia, aMCI patients, and cognitively healthy controls) on BDNF serum levels were performed using univariate analyses of variance (ANOVA). Pearson correlation coefficients were calculated to explore relationships between biochemical and clinical data. The level of statistical significance was set at p<0.05.ResultThe results showed that BDNF serum levels are decreased in AD as compared to aMCI patients (p < .05). In addition, there was a positive correlation between PAI‐1 and BDNF serum levels (r = .190, p < .05). Furthermore, PAI‐1/BDNF ratio was significantly increased in AD patients as compared to aMCI (p < .001) and controls (p < .001). Lastly, PAI‐1/BDNF ratio negatively correlated with MMSE score (r = ‐.508, p < .001).ConclusionThese data suggest that in AD a reduction of plasmin caused by PAI‐1 may negatively affect the production of BDNF and promote disease progression. Our results also demonstrate that the PAI‐1/BDNF ratio is increased in AD patients compared with aMCI and controls. They also suggest that this ratio could be used as a marker of AD in a state of overt cognitive impairment, as supported by the strong negative correlation between PAI‐1/BDNF ratio and MMSE.