Targeting the Reelin signaling pathway or the astrocyte program associated with cognitive resilience holds significant therapeutic implications for Alzheimer's disease. The Reelin signaling pathway, which has been implicated in modulating the vulnerability of excitatory and inhibitory neurons in specific brain regions, could be a promising target for therapeutic intervention. By enhancing Reelin signaling, it may be possible to protect vulnerable neurons from degeneration and promote their survival, thereby preserving cognitive function in Alzheimer's disease. Similarly, modulating the astrocyte program associated with cognitive resilience, particularly focusing on choline metabolism and polyamine biosynthesis, could offer a novel therapeutic approach. By promoting the neuroprotective functions of astrocytes, such as maintaining synaptic health and providing metabolic support to neurons, it may be possible to enhance cognitive resilience and slow down the progression of Alzheimer's pathology. Targeting these pathways could lead to the development of precision medicine approaches that aim to restore cellular homeostasis and promote brain health in individuals with Alzheimer's disease.