This study investigated the regulatory role of the long non-coding RNA maternally expressed gene 3 (MEG3) in tau hyperphosphorylation and insulin signaling (PI3K/AKT1/GSK3β) under high-glucose (HG)-induced neurotoxic conditions mimicking Alzheimer’s disease pathology. This evidence concerns the gene PIK3CA and early-onset autosomal dominant Alzheimer disease.