VITAMIN D IN ALZHEIMER'S DISEASE - PROPHYLAXIS OR THERAPY?

The pleiotropism of vitamin D is due to the presence of vitamin D receptor in the cells of nearly all tissues and organs within the human body, including the CNS. Multiple evidence is available to support neuroprotective properties of vitamin D. These include, for example, the presence of 25(OH)D-lot-hydroxylase, an enzyme responsible for production of calcitriol, within the human brain. Among its other activities, calcitriol modifies production and release of neurotrophic factors, affects expression of genes associated with GABAergic signaling and stimulates biosynthesis of catecholamines. Antioxidative and anti-inflammatory properties were also demonstrated in research studies. By confronting the known pathomechanisms of Alzheimer's disease (AD) and the mechanism of action of vitamin D, one may propose that systemic insufficiency of vitamin D is a potential risk factor of AD. Studies conducted to date confirm the inverse relationship between serum calcidiol levels and the risk of dementia diseases, including AD. Elevated cerebrospinal fluid level of VDBP, a vitamin D binding protein that is also responsible for elimination of P-amyloid peptide (AP), a pathogenic factor characteristic for AD, is considered to be a potential marker of AD. Reduction in AP levels within the CNS is the most important therapeutic target in the treatment of AD. Animal studies confirmed the impact of vitamin D-enriched diet on the reduction in amyloid deposits, AP peptide levels and inflammatory reactions as well as on the increase in the level of neurotrophic factor within the brains of AP protein precursor (APPP) - transgenic mice. In case of AD, the purposefulness of initiating treatment before the onset of clinical symptoms is being highlighted. Vitamin D is worth consideration since by inducing the expression of VDR gene it leads, among others, to the silencing of the transcription of the gene encoding the AOAPP and thus inhibits its cleavage into peptides that form amyloid deposits. Despite the fact that at current state vitamin D can hardly be considered a therapeutic agent with an established efficient dose in AD, authors of studies suggest that it is important in AD prophylaxis in elderly patients with age-related reduction of serum calcidiol lev- els.