Apolipoprotein A (ApoA) proteins, ApoA-I, ApoA-II, ApoA-IV, and ApoA-V, play critical roles in lipid metabolism, neuroinflammation, and blood–brain barrier integrity, making them pivotal in neurological diseases such as Alzheimer’s disease (AD), stroke, Parkinson’s disease (PD), and multiple sclerosis (MS). This review synthesizes current evidence on their structural and functional contributions to neuroprotection, highlighting their dual roles as biomarkers and therapeutic targets. ApoA-I, the most extensively studied, exhibits anti-inflammatory, antioxidant, and amyloid-clearing properties, with reduced levels associated with AD progression and cognitive decline. ApoA-II modulates HDL metabolism and stroke risk, while ApoA-IV influences neuroinflammation and amyloid processing. ApoA-V, although less explored, is implicated in stroke susceptibility through its regulation of triglycerides. Genetic polymorphisms (e.g., APOA1 rs670, APOA5 rs662799) further complicate disease risk, showing population-specific associations with stroke and neurodegeneration. Therapeutic strategies targeting ApoA proteins, including reconstituted HDL, mimetic peptides, and gene-based approaches, show promise in preclinical models but face translational challenges in human trials. Clinical trials, such as those with CSL112, highlight the need for neuro-specific optimization. Further research should prioritize human-relevant models, advanced neuroimaging techniques, and functional assays to elucidate ApoA mechanisms inside the central nervous system. The integration of genetic, lipidomic, and clinical data offers potential for enhancing precision medicine in neurological illnesses by facilitating the generation of ApoA-targeted treatments and bridging current deficiencies in disease comprehension and therapy.

Despite its pivotal role in drug metabolism, the exact consequences of rising medica-tions count from various therapeutic drug classes on mortality outcomes amongst patients with chronic liver disease remains unexplored. In this study, we investigated the effect of different polypharmacy phenotypes on clinical outcomes including the length of hospitalization, the need for intensive care admission, and mortality in patients with chronic liver disease (CLD). Methods: This retrospective cohort study examined the impact of various polypharmacy phenotypes on clinical outcomes of patients receiving care at tertiary care centres within the Weill Cornell Medi-cine-affiliated Hamad Medical Corporation, Doha Qatar diagnosed with CLD be-tween October 2018 to August 2021. Primary outcomes include all-cause mortality, length of hospitalization, and need for intensive care unit admission. Multivariable regression models were used to assess the associations between the number of liv-er-related and non-liver-related polypharmacy and these clinical outcomes. Results: In this retrospective cohort study, 3331 participants with a median age of 50 years (interquartile range [IQR] 40–63) were included, of which 71.0% (n = 2 366) were males. The total duration of follow-up for the whole cohort was 42 772.6 per-son-days. The median length of stay (LOS) was 5.0 (0.5, 13.6) days, with 762 (22.9%) deaths among those hospitalized. About 46.2% of the study participants were on guideline-directed therapy CLD drugs. Patients with polypharmacy inclusive of liver-related drugs had a higher survival over time compared to the group without polypharmacy (log-rank p< 0.001). Each additional CLD drug is associated with a 51% reduction in mortality risk (hazard ratio [HR] 0.49, 95% CI 0.38–0.62). Conclusion: In a hospitalized cohort of patients with CLD, polypharmacy comprising of medications specific for CLD or its complications was associated with reduced all-cause mortality. However, the role of non-liver-related medications in this context remains unclear, and it is uncertain how the primary cause of liver disease could have potentially impacted these outcomes. Further studies exploring these factors are needed to better inform clinical decision-making regarding polypharmacy management in this patient population