GSAP regulates mitochondrial function through Mitochondria-associated ER membrane in the pathogenesis of Alzheimer's disease

Gamma-secretase activating protein (GSAP) plays an important role in regulating gamma-secretase activity and specificity, which contributes to the pathogenesis of Alzheimer's disease (AD) and Down syndrome. GSAP is expressed in a variety of cell types in the bain. To elucidate the molecular function of GSAP across different cell types in the brain, we performed single nuclei RNA sequencing (sn-RNAseq) on hippocampal tissues obtained from wildtype (WT) and GSAP knockout (GKO) mice. To further investigate the pathogenic function of GSAP in the AD progression, we also determined effects of GSAP gene deletion in the J20 AD mouse model through sn-RNAseq on hippocampal tissues obtained from J20;WT and J20;GKO mice. Overall design: Single nuclei RNA sequencing was performed using hippocampal tissues from WT (7-month old; 3 mice), GKO (7-month old; 3 mice), J20;WT (6-month old; 1 mouse), and J20;GKO mice (6-month old; 1 mouse).