GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_metadata_humanAD.tsv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_ad671_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_hp32_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_ad24_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_ad22rep2_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_ad22rep1_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_humanAD_RNA_seurat_object.rds.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_ad1551_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_ad13_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_hp30_filtered_feature_bc_matrix.h5ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE288nnn/GSE288063/suppl/GSE288063_hp18_filtered_feature_bc_matrix.h5primaryOK200TranscriptomicsHomo sapiens Genome binding/occupancy profiling by high throughput sequencingExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288063GEOGSEfalseSingle cell genomic and epigenomic analysis of mouse and human Alzheimer's disease (Human)Aging is the strongest risk factor for Alzheimer’s disease (AD), yet the mechanisms by which aging promotes AD progression remain incompletely understood. Chronic neuroinflammation is a hallmark of both brain aging and AD, with microglia undergoing progressive inflammatory and functional changes, but how these age-associated changes contribute to disease progression is unclear. Here, we profiled gene expression and chromatin accessibility in the hippocampus across aging and amyloid-β (Aβ) pathology, and identified progressive activation of cGAS-STING pathway and interferon-responsive microglial states that are markedly accelerated in the process. Pharmacological inhibition of STING in aged mice improved spatial memory, reduced Aβ plaque burden and shifted microglia from interferon-responsive states towards a phagocytic program associated with enhanced Aβ clearance. Mechanistically, STING activation reduced MEF2 activity and occupancy at enhancers of phagocytosis-associated genes, whereas STING inhibition restored MEF2 activity. Human AD hippocampal microglia similarly exhibited elevated IRF3 activity together with reduced MEF2C activity and nuclear availability. STING inhibition failed to preserve Aβ phagocytosis in MEF2C-deficient human iPSC-derived microglia. Together, these findings identify a cGAS–STING–MEF2 regulatory axis through which aging-associated innate immune signaling impairs microglial Aβ clearance and suggest that targeting cGAS–STING may restore protective microglial function in AD.2026/10/01GSE288063GSM8758398GSM8758397GSM8758404GSM8758414GSM8758403GSM8758406GSM8758405GSM8758411GSM8758400GSM8758410GSM8758399GSM8758413GSM8758402GSM8758401GSM8758412GSM8758408GSM8758407GSM875840924676288063Homo sapiens