engleski

Polymorphisms of the brain-derived neurotrophic factor and cognitive impairment in patients with Alzheimer’s disease and mild cognitive impairment

Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by progressive loss of cognitive function. Since there is no cure for AD, the studies of the early phases of AD, that are trying to find new biological markers that could serve as early diagnostic indicators, have pointed out the potential importance of early detection of mild cognitive impairment (MCI). MCI is a disorder that has been associated with risk for AD since it represents a transitional state between normal and pathological aging (characterized with cognitive impairments that lead to dementia). Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor family which is implicated in modulating neuronal survival, differentiation, neuroregeneration, synaptic plasticity and cognition in the brain. The aim of this study was to investigate whether selected BDNF polymorphisms: rs 6265 (Val66Met), rs11030104, rs7934165, rs1519480 and rs56164415 (C270T), are associated with cognitive impairment in patients with AD and MCI. The study included 82 patients with AD and 49 patients with MCI. Diagnosis of AD was done according to the NINCDS-ADRDA and DSM-IV criteria. Cognitive impairment was evaluated using Mini-Mental Status Examination (MMSE) and Clock Drawing Test (CDT). Genotyping was done using the TaqMan SNP Genotyping Assay. Our results showed an association between rs1519480 and MMSE scores in patients with AD (F=3.856 ; P=0.025) and MCI (F=3.270 ; P=0.047). A marginal association between MMSE scores and C270T polymorphism in patients with AD (F=3.697 ; P=0.058) was detected. Similar results were obtained using CDT scores to predicts person's cognitive abilities, indicating that AD patients differ significantly (F=4.666 ; P=0.034) in CDT scores when subdivided according to the rs1519480 genotypes. This association was marginally significant in individuals with MCI (F=3.904 ; P=0.054). An association between rs11030104 and CDT scores in AD (F=5.495 ; P=0.022) was detected. Other analysed polymorphisms were not significantly associated with MMSE or CDT scores in AD and MCI patients. The present findings confirmed a major role of BDNF in AD, and revealed a potential role of two selected BDNF polymorphisms (rs1519480 and rs11030104) in cognitive decline that is characteristic for patients with AD and MCI.

BDNF ; Alzheimer’s disease ; MCI ; cognition ; polymorphisms

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