engleski

Serotonergic and catecholaminergic system in Alzheimer’s disease

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized with progressive memory loss, learning impairment and altered behavior. The most important risk factor for AD is aging, and due to the increasing life expectancy in population worldwide, AD becomes a great public health problem with considerable social and economic costs. The etiology of AD is still unclear. Current research indicates that AD may be triggered by a multitude of internal (age, genetic makeup, oxidative damage of neurons due to overproduction of toxic free radicals, serious head injuries, brain inflammation) and external (environmental) factors. Postmortem and neuroimaging brain studies indicated various neurobiological and molecular changes in AD. Although two abnormal structures i.e. amyloid plaques-clumps and neurofribrillary tangles-clumps are hallmarks of AD, it is uncertain whether they are the cause or the byproduct of the disease. The role of the neurotransmitter systems in cognition and memory remains to be elucidated. Literature data suggest that beside the reduced function of cholinergic neurotransmitter system, the alterations of both serotonergic and catecholaminergic systems could play a role in cognitive impairment and behavioral changes in AD. The decrease in the brain and CSF concentration of serotonin (5-HT), noradrenaline and their metabolites, reduced brain 5-HT1A (raphe nuclei, hippocampus) and 5-HT2A (cerebral cortex) receptor binding, decreased 5-HT uptake into platelets and reduced platelet 5-HT concentration were found in patients with AD. In addition a beneficial effect of the supplementary treatment with selective 5-HT reuptake inhibitor, fluoxetine, on daily living and functioning in rivastigmine treated patients with AD was also reported.These central and peripheral neurobiological changes could be related to the modification of genes encoding for proteins involved in the serotonergic and catecholaminergic neurotransmission. Genetic investigations suggested the role of serotonergic 5-HT2A and 5-HT2C receptors gene polymorphisms in the development of behavioral and psychological symptoms of AD. Particular interest has been devoted to catechol-O-methyl transferase (COMT) that has an important role in dopamine breakdown, while there are few studies focusing on dopamine-beta-hydroxylase (DBH) activity in AD. Our recent study have shown lower plasma DBH activity in patients with AD compared to healthy controls, that was independent of the presence of psychotic features and of the genetic variants in DBH gene. The identification of reliable pre-symptomatic biochemical markers and/or genetic variations, associated with the neurotransmitters’ systems, represents a promising approach for the recognition of individuals vulnerable to development of AD, as well as for detection of susceptibility gene(s), whose protein product(s) could be crucial to the occurrence of the disease particularly for the identification and treatment of AD in the early stage.

Alzheimer’s disease ; COMT ; DBH ; platelet serotonin ; platelet MAO-B

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