Core Viewpoint - The research highlights the significant role of the ABCA7 gene in Alzheimer's disease risk, particularly through its rare functional loss mutations and their impact on phosphatidylcholine metabolism and mitochondrial function in neurons [3][4][10]. Group 1: Genetic Risk Factors - APOE4 is identified as the strongest genetic risk factor for Alzheimer's disease, increasing the risk by 3 times with one copy and 8-12 times with two copies [3]. - ABCA7 gene mutations, particularly those causing functional loss, double the risk of developing Alzheimer's compared to non-carriers [3]. Group 2: Mechanisms of ABCA7 - ABCA7 protein is crucial for lipid transport and maintaining membrane asymmetry in the brain, with its dysfunction linked to amyloid protein deposition and increased neuroinflammation [6]. - The study utilized brain tissue samples from the ROSMAP study, focusing on 12 patients with ABCA7 functional loss mutations to explore the genetic impact on Alzheimer's risk [6][7]. Group 3: Cellular Impact and Interventions - Single-nucleus RNA sequencing revealed extensive gene expression changes in various neuronal cell types associated with ABCA7 mutations, affecting lipid metabolism and mitochondrial function [7]. - Supplementation with cytidine diphosphate-choline (CDP-choline) was shown to reverse the negative effects of ABCA7 mutations on neurons, restoring mitochondrial function and reducing oxidative stress [8][10].