Alzheimer's disease (AD) is the most common type of dementia, but it is very difficult to diagnose with certainty, so many AD studies have attempted to find early and relevant diagnostic markers. Regulated upon activation, normal T cell expressed and secreted (RANTES, also known as C-C chemokine ligand) is a chemokine involved in the migration of T cells and other lymphoid cells. Changes in RANTES levels and its expression in blood or in cerebrospinal fluid have been reported in some neurodegenerative diseases, such as Parkinson's disease and multiple sclerosis, but also in metabolic diseases in which inflammation plays a role. The aim of this observational study was to assess RANTES levels in peripheral blood as clinical indicators of AD. Plasma levels of RANTES were investigated in 85 AD patients in a relatively early phase of AD (median 8.5 months after diagnosis; 39 men and 46 women; average age 75.7 years), and in 78 control subjects (24 men and 54 women; average age 66 years). We found much higher plasma levels of RANTES in AD patients compared to controls. A negative correlation of RANTES levels with age, disease duration, Fazekas scale score, and the medial temporal lobe atrophy (MTA) score (Scheltens's scale) was found in AD patients, i.e., the higher levels corresponded to earlier stages of the disease. Plasma RANTES levels were not correlated with cognitive scores. In AD patients, RANTES levels were positively correlated with the levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α, which is consistent with the well-known fact that AD is associated with inflammatory processes. RANTES levels were also positively correlated with insulin levels in AD patients, with insulin resistance (HOMA-R) and pancreatic beta cell function (HOMA-F). This study evaluated several clinical and metabolic factors that may affect plasma levels of RANTES, but these factors could not explain the increases in RANTES levels observed in AD patients. Plasma levels of RANTES appear to be an interesting peripheral marker for early stages of AD. The study was approved by the Ethics Committee of Institute of Endocrinology, Prague, Czech Republic on July 22, 2011.
- Klíčová slova
- Alzheimer’s disease, RANTES, biomarker, central nervous system, cognitive impairment, inflammation,
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) is the most common type of dementia, with a prevalence that is rising every year. AD is associated with type 2 diabetes mellitus (T2DM) and insulin resistance, and is therefore sometimes called "type 3 diabetes mellitus". The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism-gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT). Our study included 550 women with former GDM and 717 control women, 392 patients with T2DM and 180 non-diabetic controls, and 117 patients with IGT and 630 controls with normal glucose tolerance. Genotyping analysis was performed using specially-designed TaqMan assays. No significant associations of the genetic variants rs744373 in BIN1, rs11136000 in CLU, or rs3818361 in CR1 were found with GDM, T2DM or IGT, but rs3851179 in PICALM was associated with an increased risk of GDM. The frequency of the AD risk-associated C allele was significantly higher in the GDM group compared to controls: OR 1.21; 95% CI (1.03-1.44). This finding was not apparent in T2DM and IGT; conversely, the C allele of the PICALM SNP was protective for IGT: OR 0.67; 95% CI (0.51-0.89). This study demonstrates an association between PICALM rs3851179 and GDM as well as IGT. However, elucidation of the possible role of this gene in the pathogenesis of GDM requires further independent studies.
- Klíčová slova
- Alzheimer’s disease, Gestational diabetes mellitus, Glucose metabolism, Impaired glucose tolerance, Polymorphisms, Type 2 diabetes mellitus,
- MeSH
- adaptorové proteiny signální transdukční krev genetika MeSH
- alely MeSH
- Alzheimerova nemoc komplikace genetika MeSH
- běloši genetika MeSH
- diabetes mellitus 2. typu genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetická variace MeSH
- genetické asociační studie metody MeSH
- gestační diabetes genetika metabolismus MeSH
- jaderné proteiny krev genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- klusterin krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- monomerní proteiny vytvářející klathrin krev genetika MeSH
- nádorové supresorové proteiny krev genetika MeSH
- odds ratio MeSH
- porucha glukózové tolerance genetika metabolismus MeSH
- receptory komplementu 3b krev genetika MeSH
- rizikové faktory MeSH
- senioři MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adaptorové proteiny signální transdukční MeSH
- BIN1 protein, human MeSH Prohlížeč
- CLU protein, human MeSH Prohlížeč
- CR1 protein, human MeSH Prohlížeč
- jaderné proteiny MeSH
- klusterin MeSH
- monomerní proteiny vytvářející klathrin MeSH
- nádorové supresorové proteiny MeSH
- PICALM protein, human MeSH Prohlížeč
- receptory komplementu 3b MeSH
