Donepezil, a compound clinically indicated as first-line treatment to slow cognitive decline and dementia, was selected because chronic alcohol usage is associated with dementia and Alzheimer’s disease, and we identified changes in neurodegenerative proteins (e.g., phospho-tau isoforms and Aβ1-42) in proteomic spatial profiling in EtOH-exposed compared to control organoids. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.