Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study

Objective: Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology. Methods: Genome-wide association studies were employed to identify single nucleotide polymorphisms (SNPs) showing significant correlations with osteocalcin. Subsequently, A two-sample Mendelian randomization analysis was conducted utilizing the inverse-variance-weighted (IVW) technique to assess the causal relationship between osteocalcin and various types of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and vascular dementia (VD). This approach aimed to minimize potential sources of confounding bias and provide more robust results. Multivariable MR (MVMR) analysis was conducted to adjust for potential genetic pleiotropy. Results: The study employed three SNPs, namely rs71631868, rs9271374, and rs116843408, as genetic tools to evaluate the causal association of osteocalcin with dementia. The IVW analysis indicated that osteocalcin may have a potential protective effect against AD with an odds ratio (OR) of 0.790 (95 % CI: 0.688–0.906; P < 0.001). However, no significant relationship was observed between osteocalcin and other types of dementia. Furthermore, the MVMR analysis indicated that the impact of osteocalcin on AD remained consistent even after adjusting for age-related macular degeneration and Type 2 diabetes with an OR of 0.856 (95 % CI: 0.744–0.985; P = 0.030). Conclusions: Our findings provide important insights into the role of osteocalcin in the pathogenesis of AD. Future research is required to clarify the underlying mechanisms and their clinical applications

Serum Calcium is Related to the Degree of Artery Stenosis in Acute Ischemic Stroke

Background/Aims: Acute ischemic stroke is caused by stenosis of artery supplying to brain. We aimed to detect some metabolites in the serum that would be related to the degree of artery stenosis and to analyze potential mechanisms. Methods: Patients diagnosed with acute ischemic stroke were divided into two groups according to their degree of artery stenosis (which was determined by computed tomographic angiography): a mild group (stenosis ≤ 30%) and a severe group (stenosis &#x3e; 30%). Serum from these patients was collected, and we focused on the differences in the concentrations of calcium, uric acid, low density lipoprotein and homocysteine. The dataset GSE11583 from the Gene Expression Omnibus database was analyzed to find the potential mechanism using bioinformatics methods. Results: Among the four metabolites, the only difference that reached significance between the two groups was in the concentration of calcium in serum (2.27±0.08 mmol/L vs 2.21±0.08 mmol/L). By comparing the gene expression levels between normal endothelial cells and adaptive remodeling endothelial cells in GSE11583, we identified 51 upregulated and 40 downregulated genes in adaptive remodeling endothelial cells. The gene set enrichment analysis revealed that upregulated genes were enriched in a phosphatidylinositol signaling system, which is closely involved in the calcium signaling pathway. Conclusion: Our results suggest that the concentration of serum calcium is higher in patients with more severe artery stenosis lesions and that the phosphatidylinositol signaling system is a key biological pathway involved in this process

Additional file 2: of Characteristics of cervical sagittal parameters in healthy cervical spine adults and patients with cervical disc degeneration

Original data-DG group. The Parameters data in the Degeneration Group. (XLSX 13 kb