Apolipoprotein E agon 
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  • ||||||||||  Biomarker, Preclinical, Journal:  Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia. (Pubmed Central) -  Apr 24, 2024   
    Moreover, an association emerged between age at disease onset and plasma GFAP (p = 0.021) and pTau181 (p < 0.001) levels. Plasma GFAP, NfL and pTau 181 are promising biomarkers in the diagnosis of the prodromic stages and prognosis of dementia.
  • ||||||||||  Journal:  Global O-glycoproteome enrichment and analysis enabled by a combinatorial enzymatic workflow. (Pubmed Central) -  Apr 24, 2024   
    Because many of the proteins that contained unannotated O-glycosylation sites have been extensively studied, we wished to confirm glycosylation at these sites in a targeted fashion. Thus, we analyzed selected purified proteins (kininogen-1, fetuin-A, fibrinogen, apolipoprotein E, and plasminogen) in independent experiments and validated the previously unknown O-glycosites.
  • ||||||||||  Journal:  Identification of metabolic pathways and key genes associated with atypical parkinsonism using a systems biology approach. (Pubmed Central) -  Apr 23, 2024   
    The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.
  • ||||||||||  anacetrapib (MK-0859) / Merck (MSD)
    Preclinical, Journal:  CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice. (Pubmed Central) -  Apr 22, 2024   
    Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice...In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.
  • ||||||||||  Preclinical, Journal, IO biomarker:  DFMG decreases angiogenesis to uphold plaque stability by inhibiting the TLR4/VEGF pathway in mice. (Pubmed Central) -  Apr 22, 2024   
    Immunohistochemical assay findings indicated a significant inverse relationship between miR-140 expression and TLR4 expression in ApoE knockout mice subjected to a high-fat diet. The study observed a close association between DFMG inhibitory effects on angiogenesis and plaque stability in AS, and the inhibition of the TLR4/NF-?B/VEGF signaling pathway, negatively regulated by miR-140.
  • ||||||||||  Assessment of T Cell Responses in Atherogenesis using AFK Mouse Model (Exhibit Hall F1; Poster Board Number: B573) -  Apr 20, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_2737;    
    It can facilitate research on immunology of atherosclerosis and assessment of athero-protective efficacy of immunotherapy. The possibility of using it in designing and evaluating novel anti-atherosclerosis modalities resetting the balance between Teff and Treg cells emerges.
  • ||||||||||  Journal:  The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD. (Pubmed Central) -  Apr 19, 2024   
    VAV3 overexpression was observed to improve glucose homeostasis as well as attenuate hepatic cholesterol accumulation in vivo. In conclusion, the STAT3/VAV3 signaling pathway might play a significant role in MAFLD by regulating glucose and cholesterol metabolism, and VAV3 might be a potential therapeutic strategy which could consequently ameliorate MAFLD.
  • ||||||||||  Review, Journal:  Alzheimer's Disease in Lebanon: Exploring Genetic and Environmental Risk Factors-A Comprehensive Review. (Pubmed Central) -  Apr 19, 2024   
    This review points out the importance of genetic mapping in the understanding of disease pathology which is crucial for the emergence of novel diagnostic tools. Hence, we establish a rigid basis for further research to identify the most influential genetic and environmental risk factors for the purpose of using more specific diagnostic tools and possibly adopting a local management protocol.
  • ||||||||||  Journal:  APOE and familial hypercholesterolemia. (Pubmed Central) -  Apr 19, 2024   
    Hence, we establish a rigid basis for further research to identify the most influential genetic and environmental risk factors for the purpose of using more specific diagnostic tools and possibly adopting a local management protocol. Therefore, APOE gene should be considered a candidate locus along with LDLR, APOB, and PCSK9 to be investigated in the genetic diagnosis of familial hypercholesterolemia.
  • ||||||||||  Review, Journal:  Application of CRISPR/Cas9 System in the Treatment of Alzheimer's Disease and Neurodegenerative Diseases. (Pubmed Central) -  Apr 19, 2024   
    Finally, we discussed various applications of the CRISPR/Cas-9 system in Alzheimer's disease. Today, using CRISPR/Cas-9 technology, scientists create Alzheimer's disease models that have a more realistic phenotype and reveal the processes of pathogenesis; following the screening of defective genes, they establish treatments for this disease.
  • ||||||||||  Journal:  REM sleep is reduced in late middle-aged and older APOE4 allele carriers. (Pubmed Central) -  Apr 18, 2024   
    Today, using CRISPR/Cas-9 technology, scientists create Alzheimer's disease models that have a more realistic phenotype and reveal the processes of pathogenesis; following the screening of defective genes, they establish treatments for this disease. Our results show that APOE4 carriers exhibit lower REM sleep duration, including in cognitively unimpaired individuals, possibly resulting from early neurodegenerative processes in regions involved in REM sleep generation and maintenance.
  • ||||||||||  Journal:  Vascular Heparan Sulfate and Amyloid-? in Alzheimer's Disease Patients. (Pubmed Central) -  Apr 17, 2024   
    Overall, these findings reveal potential intricate interplay between HS, A?, ApoE, and vascular pathology in AD, thereby underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further study of the underlying mechanisms may present novel therapeutic avenues for AD treatment.
  • ||||||||||  Journal:  Constitutive NOS Production Is Modulated by Alzheimer's Disease Pathology Depending on APOE Genotype. (Pubmed Central) -  Apr 17, 2024   
    Increased eNOS could represent compensative vasodilation to face progressive A?-induced vasoconstriction in APOE ?3, while nNOS could represent the activation of NO-mediated plasticity strategies in the same group. Our results confirm previous findings that the APOE genotype is linked with different vascular responses to AD pathology.
  • ||||||||||  Journal:  Phosphatidylglycerol Acts as a Switch for Cholesterol-Dependent Membrane Binding of ApoE Signal Peptide. (Pubmed Central) -  Apr 17, 2024   
    To the best of our knowledge, this is the first report of modulation of the affinity of a peptide for a membrane by a neighboring lipid rather than by the lipid-binding domain of the peptide. Our findings revealed a novel role of lipid diversity in modulating the membrane binding of the ApoE signal peptide and its potential implications in the unidirectional trafficking of a newly synthesized protein from the ribosomes to the endoplasmic reticulum.
  • ||||||||||  disulfiram / Generic mfg.
    Preclinical, Journal:  Disulfiram Reduces Atherosclerosis and Enhances Efferocytosis, Autophagy, and Atheroprotective Gut Microbiota in Hyperlipidemic Mice. (Pubmed Central) -  Apr 17, 2024   
    Our findings revealed a novel role of lipid diversity in modulating the membrane binding of the ApoE signal peptide and its potential implications in the unidirectional trafficking of a newly synthesized protein from the ribosomes to the endoplasmic reticulum. Taken together, our data show that disulfiram can simultaneously modulate several atheroprotective pathways in a GsdmD-dependent as well as GsdmD-independent manner.
  • ||||||||||  Journal:  Endothelial NLRP3 inflammasome regulation in atherosclerosis. (Pubmed Central) -  Apr 16, 2024   
    Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.
  • ||||||||||  Journal:  Prevalence of Dysbetalipoproteinemia in the UK Biobank According to Different Diagnostic Criteria. (Pubmed Central) -  Apr 16, 2024   
    This study reported for the first time the prevalence of DBL in the UK Biobank according to genetic ancestry. Furthermore, we provided the first external validation of different diagnostic criteria for DBL in a large population-based cohort and highlighted the fact that these criteria should not be used to diagnose DBL alone but should rather be used as a first screening step to determine which individuals may benefit from genetic testing to confirm the diagnosis.