Disrupted lipid homeostasis as a pathogenic mechanism in ABCA7-associated Alzheimer's disease risk - PubMed
7 hours ago
- #Lipid Metabolism
- #Alzheimer's Disease
- #Genetic Risk Factors
- The ABCA7 gene encodes a lipid transporter linked to increased Alzheimer's disease (AD) risk, with a specific 44-base pair deletion (rs142076058) being a strong risk factor in individuals of African ancestry.
- The truncated ABCA7 protein localizes similarly to the wild type at endoplasmic reticulum and plasma membranes but causes significant lipid droplet accumulation in HepG2 cells and iPSC-derived neurons.
- The deletion also reduces mitochondrial membrane potential in iPSC-derived neurons, indicating disrupted lipid and mitochondrial homeostasis as a key pathogenic mechanism contributing to AD risk.