摘要The entorhinal cortex(EC)-hippocampal(HPC)circuit is particularly vulnerable to Alzheimer's disease(AD)pathol-ogy,yet the underlying molecular mechanisms remain unclear.By employing the high-depth sequencing strategy Smart-seq2,we tracked gene expression changes across various neuron types within this circuit at different stages of AD pathology.We observed a decrease in the extent of gene expression changes in AD versus wild-type(WT)mice as the disease advanced.Functionally,we demonstrate that both mitochondrial and ribosomal pathways were increasingly activated,while neuronal pathways were inhibited with AD progression.Our findings indicate that the reduction of EC-stellate cells disrupts Meg3-mediated energy metabolism,contributing to energy dysfunction in AD.Additionally,we identified GFAP-positive neurons as a distinct population of disease-associated neurons,exhibiting a loss of neuronal-like characteristics,alongside the emergence of glia-and stem-like features.The num-ber of GFAP-positive neurons increased with AD progression,a trend consistently observed in both AD model mice and AD patients.In summary,this study identifies and characterizes GFAP-positive neurons as a novel subtype of disease-associated neurons in AD pathology,providing insights into their potential role in disease progression.