Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer’s disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting P. gingivalis to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood–brain barrier disruption, neuroinflammation, and neuronal damage. P. gingivalis-derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting P. gingivalis virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into P. gingivalis-mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management.

Soluble HLA-G, its diagnostic and prognostic value and potential target molecule for future therapy in cancer

Background: Human leukocyte antigen G (HLA-G) belongs to nonclassical HLA I molecule involving in the suppression of immune response. Besides its profound effect to induce fetal tolerance, HLA-G expression has been associated with allograft acceptance. For the regulation of HLA-G levels, polymorphic sites within the 3′ untranslated region (3′UTR) are of crucial importance. The aim of the study was to analyze the association between several HLA-G 3′UTR variants (+3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, +3187A/G, and +3196C/G), soluble HLA-G (sHLA-G) level, and kidney graft outcome in the Slovak Caucasian population. Methods: We investigated 69 kidney transplant recipients (45 males, 24 females) of age 27–65 years. Out of this group, 37 recipients developed acute rejection that was biopsy proven. Recipient’s plasma was obtained at 1 day before transplantation and analyzed by ELISA. The HLA-G 3′UTR polymorphisms were typed by direct sequencing. Results: In the recipients with stable allograft function, significantly higher values of sHLA-G were found in the homozygous +3010GG, +3142CC, +3187GG, and +3196CC carriers in comparison to the acute rejection recipients (P = 0.01-0.05). Conclusion: The study demonstrated genetic association between HLA-G 3′UTR variants and sHLA-G level in kidney recipients leading to graft acceptance. We suggest to monitor the pretransplantation sHLA-G level as additional marker to predict kidney graft outcome. Abbreviations: AMR: Antibody-mediated rejection; APC: antigen-presenting cell; CD: cluster of designation; del: deletion; HLA: human leukocyte antigen; ILT: immunoglobulin-like transcript; ins: insertion; KIR: killer-cell immunoglobulin-like receptor; NK: natural killer; sHLA-G: soluble HLA-G; SNP: single nucleotide polymorphism; TCMR: T cell-mediated rejection; URR: upstream regulatory region; UTR: untranslated region

Alzheimer’s disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin moleculeα4β1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in theITGA4gene encoding theα4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped forITGA4gene SNP polymorphism rs113276800 (−269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for theAPOE-ε4, which is a known genetic factor associated with increased risk of AD developing.ITGA4polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P≤0.05). Following theAPOE-ε4 stratification of study groups, the association remained significant only inAPOE-ε4 noncarriers. Our study suggests a novel association ofITGA4+3061A/G polymorphism with AD and its possible contribution to the disease pathology.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood‐brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP‐2 and MMP‐3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR‐RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (‐1306 C>T) and MMP3 rs3025058 (‐1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44 ± 6.28 vs. 76.36 ± 6.39, p = 0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61 ± 5.88 vs. 78.57 ± 6.79, p = 0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.

Background: The function of the MHC class I polypeptide-related sequence A (MICA) gene, which belongs to the MHC class I chain-related genes, is to trigger cytolysis of target cells mediated by NKG2D receptor recognition in NK (Natural Killer) cells and CD8 T-lymphocytes. The MICA gene has a high degree of polymorphism, especially observed in exons 2–5. MICA allelic diversity has been reported in association with some autoimmune diseases such Behcet's disease, psoriasis and diabetes, as well as with organ rejections. Aim: The aim of this study was to analyse MICA gene polymorphism in the Slovak population, to establish frequencies of MICA alleles and to compare the results with those found in other Western Eurasian populations. No such study has been performed previously in the Slovak population. Subjects and methods: This study examined DNA samples from 124 unrelated Slovak individuals (51 women and 73 men with an average age of 40.3 years) using direct sequencing of MICA exons 2–5. Allele and genotype frequencies were calculated by direct counting and statistical analysis was carried out using Arlequin software. Results: This study identified 15 out of 71 MICA alleles. The most frequent allele was MICA^*008 (37.1%) followed by alleles MICA^*002 (16.5%) and MICA^*009 (11.3%). The rarest alleles were MICA^*027, MICA^*006 (both 0.8%) and MICA^*057 (0.4%), respectively. The most frequent genotypes were 008/008 and 008/002, both with a frequency of 13.7%. Exon 5 microsatellite polymorphism screening revealed five MICA alleles, namely A4, A5, A5.1, A6 and A9. The most frequent was allele A5.1 (37.1%) and the rarest A5 (8.1%). Finally it was found that haplotype MICA*008 A5.1 was the most frequent (37.1%). Conclusion: A comparison of these results with those reported in the literature revealed similarity in MICA polymorphism to that found in other Western Eurasian populations. The data will be useful for further association studies on MICA polymorphism and its function.