Neurodegenerative disorders such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are characterized by a progressive loss of neurons, correlating with loss of motor and cognitive function that has an impact on global health. Diagnosis of these diseases in clinical settings is generally delayed due to reliance on clinical features and diagnostic criteria that focus on symptomatic stages of the neurodegenerative disorder. Growing evidence suggests that pathological activity at a molecular level can occur years before the onset of symptoms. This narrative review focuses on recent progress in fluid, imaging, genetic, and multi-omics as well as digital biomarkers, with an emphasis on their diagnostic implementation, feasibility, value, and translation into clinical settings. In AD, cerebrospinal fluid and plasma biomarkers such as Glial Fibrillary Acid Protein (GFAP), Aβ1–42/Aβ1–40 ratios, and phosphorylated tau isomers (p-tau181, p-tau217) have been shown to have promising diagnostic relevance and utility. Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking-Induced Conversion (RT-QuIC) have shown high diagnostic specificity for detecting α-synuclein seeding activity, accurately distinguishing synucleinopathies, which are of particular interest in PD. Corresponding imaging biomarkers, including structural and functional MRI, Positron Emission Tomography (PET), and multimodal imaging, provide complementary insight into the relevance of disease-stage categorization. Multi-omics profiling and digital biomarkers, including wearable sensors, speech and gait analysis, and electroencephalography combined with artificial intelligence-driven pattern recognition, further broaden the biomarker terrain toward continuous, precision-based monitoring of neurodegeneration. Despite significant progress, limitations remain in standardization, biological heterogeneity, and validation of relevant findings. Ethical considerations related to preclinical diagnosis also require considerable premeditation. The change toward the implementation of a multimodal framework has the potential to shift neurodegenerative disease diagnosis from symptomatic late-stage diagnosis to early, molecularly mechanistic-driven medical aftermath.
Introduction Identification of non-invasive biomarkers reflecting glycaemic status and microvascular risk remains a priority in type 2 Diabetes Mellitus (T2DM). α 2 -Macroglobulin (α 2 MG), a high-molecular-weight acute-phase glycoprotein involved in inflammatory regulation, increases in hyperglycaemic states and may be detectable in saliva. This study evaluated the association of salivary α 2 MG with glycaemic control and Diabetic Retinopathy (DR). Methods In this cross-sectional study (January–October 2025), 130 adults were categorised as healthy controls (n=26), controlled T2DM (n=52), and uncontrolled T2DM (n=52). Unstimulated saliva was collected and α 2 MG quantified by enzyme-linked immunosorbent assay. Glycaemic indices, lipid parameters, insulin levels, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and DR status were assessed. Correlation, multivariable regression, and Receiver Operating Characteristic (ROC) analyses were performed. Results Salivary α 2 MG concentrations were significantly higher in uncontrolled T2DM than in controlled T2DM and controls ( P < 0.001). α 2 MG correlated positively with fasting glucose, postprandial glucose, glycated haemoglobin (HbA1c), triglycerides, insulin levels, and HOMA-IR. Participants with DR had significantly higher α 2 MG concentrations than those without retinopathy ( P < 0.001). ROC analysis showed modest discrimination for identifying uncontrolled T2DM, with an optimal cut-off of 764 ng/mL (sensitivity 76.15%; specificity 70%). Discussion These findings suggest salivary α 2 MG reflects both metabolic dysregulation and microvascular injury, supporting its potential relevance as a non-invasive adjunct biomarker in diabetes monitoring, complication risk assessment, and microvascular risk stratification in T2DM. Conclusion Salivary α 2 MG was associated with glycaemic dysregulation and DR in T2DM, supporting its potential as a non-invasive adjunct biomarker. Its ease of collection may facilitate metabolic assessment, particularly in resource-limited settings, pending longitudinal validation.
Introduction Thalassemia, a group of recessively inherited disorders, is characterized by persistent anemia of varying severity and diminished or nonexistent hemoglobin synthesis. Approximately 80 - 90 million individuals, including approximately1.5 percent of the population, are affected by β thalassemia. Beta thalassemia is associated with more than 200 identified mutations. The elevated prevalence of thalassemia in the area extending from sub-Saharan Africa to the Middle East can be attributed to the evolutionary link between malaria resistance and the thalassemia carrier state. Methods This study included 100 patients (50 males and 50 females) with β-thalassemia major (β-TM). The subjects were classified into two groups: Group 1 (G1) included individuals diagnosed with a body mass index (BMI) below 30, while Group 2 (G2) included individuals with a BMI above 40. A third group of healthy individuals without any known medical conditions was included as a control group (G3). Blood samples were collected, and an enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of P-selectin and PSGL-1. Results The results showed that PSGL-1 may be a more reliable diagnostic biomarker. P-selectin was also found to be useful, although less effective, particularly in identifying obesity-related conditions in individuals with lower BMI. Discussion This study aimed to evaluate P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) as potential biomarkers in Iraqi patients with β-thalassemia major and to assess the effect of obesity on their serum levels. Conclusion These findings may help improve the understanding of the relationship between obesity and hematological complications in patients with β-thalassemia.
Introduction Neonatal sepsis is one of the major causes of morbidity and mortality in newborns, particularly in developing countries. Zinc levels are involved in the outcome of sepsis, as they influence the function of the immune system and cytokine activity such as Interleukin-6 (IL-6). Data regarding the association between zinc and neonatal sepsis remain limited. Methods This observational, analytical, cross-sectional study investigated the correlation between zinc and IL-6 in neonates with neonatal sepsis. Participants were divided into a control group and a sepsis-risk group. Serum samples were analyzed for zinc by titration and for IL-6 by enzyme immunoassay. Results A total of 69 neonates were recruited and were divided into a control group of 34 neonates and a group at risk of sepsis of 35 neonates. Zinc levels in the sepsis-risk group were significantly lower than in the control group (57.34 ± 8.89 µg/dL vs. 80.47 ± 13.80 µg/dL, p<0.001). There was no significant difference in IL-6 levels between the two groups. A significant negative correlation was observed between serum zinc levels and the risk of sepsis (correlation coefficient = -0.548, P < 0.05). Discussion This study demonstrates that lower serum zinc levels are associated with a higher prevalence of sepsis risk in neonates, suggesting that susceptibility to sepsis in the early neonatal period may be associated with zinc status. The absence of a significant difference in IL-6 levels between groups may have been influenced by the timing of sample collection, as subjects were identified based on sepsis risk factors rather than confirmed infection. Conclusion Neonates at risk for sepsis had lower serum levels of zinc but not the level of IL-6 when compared with healthy neonates. These study findings support a relationship between the neonate's zinc status and its early immune status. Further research is required to establish its effectiveness in a clinical setting.
Failure of dental implants due to inadequate osseointegration continues to pose a major clinical issue, with increasing evidence suggesting that systemic and genetic factors play a role in the outcomes. It is proposed that vitamin D deficiency and genetic variations, such as those in the vitamin D receptor (VDR) gene, may affect bone metabolism and the success of implants. This case-control study aimed to evaluate the association of serum vitamin D levels and VDR gene polymorphism (SNP rs228570) with dental implant osseointegration success or failure. A case-control study with 42 cases of implant failure and 42 controls with successful osseointegration was conducted in patients aged 31–60 years. Sociodemographic, clinical, and periodontal parameters were analyzed, and VDR SNP rs228570 was genotyped using real-time PCR, and serum vitamin D, TNF, and IL-6 levels were measured. Statistical analysis was performed using SPSS v28.0, with univariate and multivariable logistic regression with significance (p < 0.05). No significant association was found between VDR gene polymorphism (SNP rs228570) and implant failure (p > 0.05). However, there is a significant association between higher vitamin D levels and successful osseointegration. Vitamin D levels were significantly higher in the successful group (36.85 ng/ml ± 11.55) compared to the failed group (17.03 ng/ml ± 9.16) (p < 0.001). Clinical parameters revealed significant differences, with the successful group showing lower bleeding on probing (BOP) at 25.15% (SD ± 5.31) compared to 42.46% (SD ± 7.59) in the failed group (p < 0.001) and a shallower probing depth of 2.21 mm (SD ± 0.85) compared to 5.62 mm (SD ± 1.32) in the failed group (p < 0.001). Biochemical markers such as TNF and IL-6 did not show significant differences between the groups, P-value = 0.181 and 0.186, respectively. The study highlights the importance of vitamin D levels and clinical parameters such as BOP and PD in predicting osseointegration outcomes. The study highlights the importance of vitamin D levels and clinical parameters such as BOP and PD in predicting osseointegration outcomes. Although VDR gene polymorphism showed no significant association with implant failure, higher vitamin D levels were positively correlated with successful osseointegration. These findings suggest that optimizing vitamin D levels and managing peri-implant health may improve dental implant success rates, emphasizing clinical over genetic predictors.
