👤 Darren E J Seah

Alzheimer disease (AD) is a progressive neurodegenerative disorder that predominantly affects the aging population. Anti-amyloid β (anti-Aβ) therapies, such as lecanemab, have been developed to slow disease progression. However, their use is occasionally associated with amyloid-related imaging abnormalities (ARIA), posing prominent clinical challenges. It has been shown that apolipoprotein E ( This retrospective study evaluated patients with AD who underwent A total of 85 patients were included in the study with rare genotypes excluded from analysis (3 patients). Among the common genotypes, e3/e4 was the most prevalent (55%). Statistical analysis revealed significant association between In this cohort of patients with AD being evaluated for lecanemab therapy, a significant association was identified between Show less

This study aims to explore the association between plasma metabolites and chronic kidney disease progression in individuals with type 2 diabetes. We performed a comprehensive metabolomic analysis in a prospective cohort study of 5144 multi-ancestral individuals with type 2 diabetes in Singapore, using eGFR slope as the primary outcome of kidney function decline. In addition, we performed genome-wide association studies on metabolites to assess how these metabolites could be genetically influenced by metabolite quantitative trait loci and performed colocalisation analysis to identify genes affecting both metabolites and kidney function. Elevated levels of 61 lipids with long unsaturated fatty acid chains such as phosphatidylethanolamines, triacylglycerols, diacylglycerols, ceramides and deoxysphingolipids were prospectively associated with more rapid kidney function decline. In addition, elevated levels of seven amino acids and three lipids in the plasma were associated with a slower decline in eGFR. We also identified 15 metabolite quantitative trait loci associated with these metabolites, within which variants near TM6SF2, APOE and CPS1 could affect both metabolite levels and kidney functions. Our study identified plasma metabolites associated with prospective renal function decline, offering insights into the underlying mechanism by which the metabolite abnormalities due to fatty acid oversupply might reflect impaired β-oxidation and associate with future chronic kidney disease progression in individuals with diabetes. Show less

G-quadruplex (G4) binding proteins regulate important biological processes, but their interaction networks are poorly understood. We report the first use of G4 as a warhead of a proteolysis-targeting chimera (G4-PROTAC) for targeted degradation of a G4-binding protein (RHAU/DHX36). G4-PROTAC provides a new way to explore G4-protein networks and to develop potential therapeutics. Show less