These FDA-approved Alzheimer’s disease therapeutics emerged through network-based targeting of glutamate receptor systems (memantine: NMDA antagonism via GRIN2A engagement) and cholinergic neurotransmission (donepezil: acetylcholinesterase inhibition enhancing synaptic acetylcholine availability), demonstrating that computational approaches can effectively identify clinically validated therapeutic mechanisms when properly integrated with CNS-focused filtering and pharmaceutical property assessment. This evidence concerns the gene ACHE and early-onset autosomal dominant Alzheimer disease.