👤 Basmah Al-Jammal

BackgroundAlzheimer's disease (AD) is the most common form of dementia, marked by progressive cognitive decline. Low-density lipoprotein cholesterol (LDL-C) has been implicated in AD pathology, but findings remain inconsistent. Apolipoprotein E4 (APOE4) status and sex may contribute to this variability.ObjectiveTo examine how LDL-C association with neurodegeneration in AD patients, differ according to APOE4 status and gender.MethodsWe stratified 106 AD patients by APOE4 status and sex into four subgroups: male APOE4+, female APOE4+, male APOE4-, and female APOE4-. Longitudinal cortical thickness changes were assessed using magnetic resonance imaging (MRI). We examined the association between LDL-C levels and cortical thinning within each subgroup.ResultsIn APOE4-positive females, higher LDL-C levels were significantly associated with accelerated cortical thinning in several regions, including the parahippocampal (β = -0.0075, p = 0.017), medial orbitofrontal (β = -0.0025, p = 0.028), fusiform (β = -0.0047, p = 0.034), posterior cingulate (β = -0.0097, p = 0.006), and inferior temporal cortices (β = -0.0085, p = 0.019). This subgroup also showed a significant association between LDL-C and MMSE decline (β = -1.409, p = 0.014) as well as longitudinal increases in cerebrospinal fluid phosphorylated tau181 (β = 0.014, p = 0.039). These effects were not observed in other subgroups.ConclusionsElevated LDL-C is associated with increased neurodegeneration and cognitive decline in female AD patients carrying the APOE4 allele. These exploratory findings highlight a subgroup-specific vulnerability to lipid-related neurodegeneration in AD and underscore the importance of considering both sex and genetic background in future studies. Show less

Hyperlipidemia is a heterogeneous disorder that refers to increased lipid levels in the blood. The purpose of this study was to investigate the molecular effects of novel carboxamide derivatives on a hyperlipidemic male rat model induced by Triton WR-1339 in comparison to fenofibrate using liver, endothelial, and adipose tissue samples. Nitrofuran-2-carboxamide derivatives were compared to fenofibrate to evaluate their molecular hypolipidemic actions. The gene expression profiles of pathways related to triglycerides including PPAR-alpha and beta-oxidation pathways were evaluated in an acute hyperlipidemia rat model using RT-PCR followed by protein-protein interaction networks that were produced using the STRING database. The three novel compounds showed a significant effect on the lipid profile. Several genes were reported to be overexpressed by Triton WR-1339, including CPT1 A in liver tissue and APOE in adipose tissue. Most of the overexpressed genes were downregulated by carboxamide derivatives, with significant decreases in CPT1 A and APOE gene expression levels. On the other hand, several genes were reported to be downregulated by Triton WR-1339, including ACOX1 in liver tissue, LPL, ACADM and ACAA2 in endothelial tissue, and LPL and ACADM in adipose tissue. Most of the downregulated genes were significantly upregulated by carboxamide derivatives. In summary, the three novel compounds were found to improve hypertriglyceridemia with significant changes in gene expression of key enzymes in lipids metabolism, mainly LPL. Show less