Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and represents a major public health challenge. With increasing life expectancy, the incidence of AD has also increased, highlighting the need for early diagnosis and improved monitoring. Traditionally, diagnosis has relied on clinical symptoms and neuroimaging; however, the introduction of biomarkers has revolutionized disease assessment. Traditional biomarkers, including the Aβ42/Aβ40 ratio, phosphorylated tau (p-Tau181, p-Tau217, and p-Tau231), total tau (t-tau), and neurofilament light chain (NfL), are fundamental for staging AD progression. Updated guidelines introduced the ATX(N) model, which extends biomarker classification to include additional promising biomarkers, such as SNAP-25, YKL-40, GAP-43, VILIP-1, progranulin (PGRN), TREM2, IGF-1, hFABP, MCP-1, TDP-43, and BDNF. Recent advancements have allowed for the detection of these biomarkers not only in CSF but also in plasma and neuron-derived exosomes, offering less invasive and more accessible diagnostic options. This review explores established and emerging biomarkers and emphasizes their roles in early diagnosis, patient stratification, and precision medicine.

Killer Ig-like Receptors (KIRs) regulate immune responses, maintaining the balance between activation and inhibition of the immune system. KIRs are expressed on natural killer cells and some CD8 T cells and interact with HLA class I molecules, influencing various physiological and pathological processes. KIRs’ polymorphism creates a variability in immune responses among individuals. KIRs are involved in autoimmune disorders, cancer, infections, neurological diseases, and other diseases. Specific combinations of KIRs and HLA are linked to several diseases’ susceptibility, progression, and outcomes. In particular, the balance between inhibitory and activating KIRs can determine how the immune system responds to pathogens and tumors. An imbalance can lead to an excessive response, contributing to autoimmune diseases, or an inadequate response, allowing immune evasion by pathogens or cancer cells. The increasing number of studies on KIRs highlights their essential role as diagnostic and prognostic biomarkers and potential therapeutic targets. This review provides a comprehensive overview of the role of KIRs in all clinical conditions and diseases, listed alphabetically, where they are analyzed.

Background: Acute ischemic stroke (AIS) remains a major cause of morbidity and mortality, with an unmet need for reliable blood-based biomarkers. Glial fibrillary acidic protein (GFAP), an astrocytic structural protein, is established in hemorrhagic stroke and traumatic brain injury, but its role in AIS remains incompletely defined. Methods: In this retrospective case-control study, we enrolled AIS patients and healthy controls. Serum GFAP was measured within 24 h using the Lumipulse G1200 automated assay. Stroke severity and outcome were assessed with the National Institutes of Health Stroke Scale (NIHSS) and functional outcome with the modified Rankin Scale (mRS). Associations with clinical measures were explored using Spearman correlation, and diagnostic accuracy was determined by ROC analysis. Results: GFAP levels were significantly higher in AIS patients than controls (median 132.9 vs. 30.0 pg/mL, p < 0.001). The ROC analysis yielded an AUC of 0.88 (95% CI 0.81–0.96). A cutoff of 71 pg/mL achieved 74% sensitivity and 92% specificity, while 150 pg/mL and 32 pg/mL optimized positive and negative predictive values (95% and 96%). GFAP was correlated with stroke severity (NIHSS, ρ = 0.37–0.40, p < 0.001) and disability (mRS, ρ = 0.48–0.49, p < 0.001). No significant differences appeared across TOAST subtypes. Conclusions: Serum GFAP is significantly elevated in AIS and demonstrates strong diagnostic and prognostic value. Integration of GFAP into clinical workflows may enhance early stroke detection and outcome prediction, supporting its role as a promising biomarker in AIS.

Neurodegenerative diseases (NDs) are increasingly considered neurometabolic disorders driven by early mitochondrial dysfunction, neuroinflammation, and synaptic alterations that precede clinical symptoms. This review summarises pre-clinical and experimental evidence suggesting that intermittent fasting (IF) may influence these early pathogenic processes by promoting metabolic switching, enhancing autophagy and mitochondrial quality control, and modulating neuroimmune pathways. We discuss recent advances in biomarker research supporting the early detection of neurodegenerative changes, including ultrasensitive analytical platforms that can identify neuronal, glial, and synaptic injury during preclinical stages. By integrating these biomarker developments with findings from human and experimental intermittent fasting studies, we highlight how high-sensitivity assays provide quantifiable insights into the neurometabolic effects of fasting. Furthermore, we discuss how precision nutrition strategies incorporating multimarker panels, phenotypic and epigenetic signatures, and longitudinal multi-omics profiling may facilitate personalised intermittent fasting protocols and improve monitoring of biological responses. Overall, these findings underscore the relevance of a clinical biochemistry perspective integrating advanced biomarker technologies to evaluate the neurometabolic effects of intermittent fasting as a potential early neuroprotective strategy for individuals at risk of neurodegeneration.

Multiple Sclerosis (MS) is a neuroinflammatory disorder in which genetic and environmental factors contribute to disease onset. Evidence implicates the inflammasome pathway in MS pathophysiology. However, the interaction between inflammasome-related genetic variants and 25-OH-vitamin D₃ (25(OH)D₃) levels remains unclear. 105 MS patients and 109 healthy controls were enrolled. Genotyping of NLRP3 (rs10754558, rs3806265) and NLRC4 (rs479333) polymorphisms was performed using real-time PCR. Serum 25(OH)D₃ levels were measured by high-performance liquid chromatography. Clinical severity was assessed using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS), annualized relapse rate (ARR), and age at onset. MS patients showed significantly lower serum 25(OH)D₃ levels than controls. Genotype distributions did not differ significantly under an additive model; however, the NLRP3 rs10754558 GG genotype was more frequent in MS patients under a recessive model and was significantly associated with disease status after adjustment for sex. Subjects carrying the GG genotype also had significantly lower serum 25(OH)D₃ levels than CC/CG carriers, independently of sex. No significant associations were observed for NLRP3 rs3806265 or NLRC4 rs479333, and none of the investigated variants was associated with EDSS, MSSS, ARR, or age at onset. The NLRP3 rs10754558 polymorphism may be associated with MS susceptibility and reduced circulating vitamin D levels, suggesting a potential link between inflammasome-related genetic variability and immunometabolic regulation in MS.

Background/Objectives: Overweight and obesity are major drivers of cardiometabolic dysfunction and increase the risk of type 2 diabetes (T2DM)and cardiovascular disease. Although lifestyle intervention remains the cornerstone of treatment, complementary strategies may provide additional benefits. The effects of Glucoerb^® and Epavin^®, administered individually or in combination, on cardiometabolic health in adults with overweight or obesity remain poorly characterized. Methods: In this prospective real-world study, 150 adults received Glucoerb^® (n = 50), Epavin^® (n = 50), or their combination (n = 50), alongside individualized nutritional counselling based on a moderately carbohydrate-restricted Mediterranean diet and standardized physical activity recommendations. Anthropometric, body composition, biochemical, and vascular parameters were assessed at baseline and after 3 months. Results: All groups showed significant improvements in body weight, body mass index (BMI), waist circumference, and fat mass (FM) (all p < 0.001). Glucoerb^® supplementation was associated with a significant reduction in HOMA-IR (−21%), whereas Epavin^® supplementation improved the lipid profile (total cholesterol −13%, triglycerides−13%, LDL cholesterol −17%, HDL cholesterol +6%). Fatty Liver Index decreased across all groups (Glucoerb^® −14%, Epavin^® −19%, combination −17%). Combined supplementation was associated with reductions in body weight (−6%) and HOMA-IR (−32%), while endothelial function improved (+19%, p = 0.017). Conclusions: These findings support further investigation of complementary multi-target plant-based strategies for cardiometabolic risk management.