Publications by authors named "To Ka Dorcas Cheung"
Aging is associated with cell senescence and is the major risk factor for AD. We characterized premature cell senescence in postmortem brains from non-diseased controls (NDC) and donors with Alzheimer's disease (AD) using imaging mass cytometry (IMC) and single nuclear RNA (snRNA) sequencing (> 200,000 nuclei). We found increases in numbers of glia immunostaining for galactosidase beta (> fourfold) and p16 (up to twofold) with AD relative to NDC.
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- Brain perfusion and blood-brain barrier integrity are compromised early in Alzheimer's disease, leading to increased vascular issues.
- Single nucleus RNA sequencing revealed that endothelial cells in Alzheimer's patients show gene expressions linked to AD susceptibility, particularly involving β-amyloid and impairments in vascular signaling.
- The study suggests that targeting vascular inflammation and enhancing angiogenesis may help reduce vascular dysfunction and potentially slow down the onset or progression of Alzheimer's disease.
Introduction: Tandem pore domain halothane-inhibited K+ channel 1 (THIK-1, coded by KCNK13) provides an upstream regulation of the activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which has been suggested as one of the key mechanisms of the pathological process in neurodegeneration mainly from in vitro and in vivo model systems studies. However, unequivocal evidence from neurodegenerative disorders has been lacking.
Objective: To investigate the involvement of the THIK-1/NLRP3 pathway in the pathological process of Alzheimer's disease (AD) and Parkinson's disease (PD).