Abstract: The present invention describes cell-based screening methods that allow for the elimination of false-positive results due to nonspecific toxicity of test compounds, while detecting those compounds that specifically modulate cellular metabolites in metabolic pathways associated with diseases and disorders, with particular regard to Alzheimer's disease. The methods are particularly suited to high-throughput screening techniques to identify compounds (drugs) that are effective in a cell-based system. The methods of the invention involve determining within a cell system the levels of both a metabolic precursor and a metabolite of interest and have broad application in high-throughput drug discovery and identification, particularly for precursor and metabolite molecules which are associated with disease and disease progression, such as Alzheimer's disease.