Phosphoglycerate dehydrogenase (PHGDH) operates through a novel RNA-binding mechanism to accelerate intracellular amyloid-beta accumulation in human brain organoids modeling sporadic Alzheimer's disease. This metabolic enzyme, previously recognized as an early biomarker, demonstrates direct involvement in the pathological cascade that precedes clinical symptoms. The discovery positions PHGDH as a convergence point between altered cellular metabolism and protein aggregation pathology. This mechanistic insight addresses a fundamental gap in understanding sporadic Alzheimer's triggers, since most research has focused on familial variants with clear genetic drivers. The RNA-binding function represents an unexpected dual role for this serine synthesis enzyme, suggesting metabolic dysfunction directly influences amyloid processing rather than merely correlating with disease progression. Brain organoid models offer advantages over traditional cell culture by preserving three-dimensional tissue architecture and cell-type interactions, though they cannot fully replicate the complexity of aging human brains. If validated in additional model systems, PHGDH's RNA-regulatory activity could reveal therapeutic targets for intervention during the asymptomatic phase when neuronal damage remains reversible.