Abca7, an ATP-binding cassette transporter, belongs to the ABC transporter gene superfamily [4,5,6,7]. It is involved in lipid homeostasis, phagocytosis, and is highly expressed in microglial cells in the brain [4,3]. Genetic studies, including genome-wide association studies (GWAS), have identified Abca7 gene variants as susceptibility loci for late-onset Alzheimer's disease (AD) [5,8]. Genetic models, such as knockout (KO) mouse models, are valuable tools to study its functions.

ABCA7 deficiency in human iPSC models leads to reduced mitochondria-related phospholipids, altered mitochondrial morphology, reduced ATP synthase activity, and exacerbated oxidative damage. These neurons also show compromised mitochondrial respiration, excess ROS generation, and decreased spontaneous synaptic firing and network formation. Similar effects are seen in synaptosomes from neuron-specific Abca7 knockout mice, suggesting that ABCA7 loss-of-function contributes to AD risk by modulating mitochondria lipid metabolism [1]. ABCA7 deficiency in other models can cause neuronal apoptosis via endoplasmic reticulum stress, increase Aβ production, and destroy microglia's ability to phagocytose and degrade Aβ, leading to reduced Aβ clearance [2].

In conclusion, Abca7 plays crucial roles in lipid metabolism, phagocytosis, and mitochondrial function. Studies using Abca7 KO mouse models have significantly contributed to understanding its role in AD pathogenesis, highlighting its importance as a potential therapeutic target for AD [1,2,5].