engleski

Genetic analysis of the brain derived neurotrophic factor Val66Met polymorphism in Alzheimer’s disease

Aims: Alzheimer’s disease (AD) is prevalent, complex and progressive neurodegenerative disorder, characterized by heavy memory losses, losses of speech, reductions of the cognitive function, altered behavior, and inabilities of decision making. AD is the most frequent cause of dementia. The genetic risk factors for AD include mutations of genes for amyloid precursor protein, presenilins, apolipoprotein E gene, but also for brain derived neurotrophic factor (BDNF). BDNF is a neurotrophin that regulates neuronal development and function, cognition, learning, mood, behavior, and stress response. Since BDNF affects cholinergic, dopaminergic, and serotonergic neurotransmission, it has a role in the etiopathogenesis of different neuropsychiatric disorders including AD. Cognitive decline is associated with reduced BDNF levels. The BDNF gene contains a common, functional polymorphism, Val66Met that produces the substitution of valine (Val) to methionine (Met). It affects intracellular trafficking and activity-dependent secretion of BDNF. The Met allele is associated with reduced delayed episodic memory, poor working memory performance and impaired hippocampal function. BDNF Val66Met polymorphism was proposed, and opposed, to be a risk factor for AD. The aim of the study was to compare the distribution of Val66Met variants in male and female healthy persons, patients with mild cognitive impairment (MCI) and patients with AD. Methods: BDNF Val66Met was genotyped with RT-PCR method from DNA extracted from blood samples obtained from 211 AD patients, 20 MCI patients and 144 healthy age-matched controls, recruited at the Psychiatric Hospital Vrapce and Department of Neurology, Clinical Hospital Centre Zagreb. AD patients were further subdivided according to the early/ late onset of AD and presence/absence of psychotic symptoms. Results and conclusion: Patients with AD, MCI, early and late onset of AD, psychotic and non-psychotic AD, and healthy persons had similar frequency of the BDNF Val66Met variants. When divided by gender, significant differences in the frequency of genotypes, and Met carriers versus Val homozygotes were detected within male or female patients with psychotic AD. Although BDNF Val66Met was not confirmed as a susceptibility factor for AD, the results suggested a possible association between Met carriers of the BDNF Val66Met, psychotic symptoms of AD and gender in AD.

brain derived neurotrophic factor; gene; Val66Met polymorphism; Alzheimer's disease

Časopis "Neurologia Croatica" indeksiran je u Neuroscience Citation Index i EMBASE/Excerpta Medica.