<p>Alzheimer disease is characterized by progressive cognitive decline driven by amyloid-β (Aβ) accumulation, tau hyperphosphorylation, synaptic loss and brain atrophy. Emerging evidence positions metabolic reprogramming encompassing impaired glucose uptake/glycolysis, mitochondrial dysfunction, redox imbalance, and altered lipid metabolism as an early and central contributor to AD pathogenesis. This review summarizes recent biochemical and translational findings linking glucose hypometabolism including reduced GLUT1/GLUT3 expression, disrupted glycolytic enzyme activity to neuronal energy failure and synaptic dysfunction, and examines how mitochondrial defects like aberrant dynamics, reduced ETC activity, and impaired mitophagy amplify reactive oxygen species (ROS) production and bioenergetic collapse. We highlight key molecular regulators AMPK, mTOR, SIRT1–PGC-1α, and insulin/PI3K–Akt signaling that coordinate neuronal energy homeostasis and show how their dysregulation creates feed-forward loops between Aβ/tau pathology and metabolic dysfunction. The review also evaluates metabolic biomarkers such as FDG-PET hypometabolism, lactate changes, metabolomic signatures and current metabolic-targeted strategies, including insulin sensitizers, intranasal insulin, mitochondrial cofactors include CoQ10, ALA, NAD⁺ precursors/SIRT1 activators, ketogenic approaches, and combined mitochondrial nutrient therapies. Finally, we discuss challenges and future directions, emphasizing the need for individualized metabolic profiling and rigorously validated multi-omics tools to translate metabolic insights into precision diagnostics and therapies. Together, the evidence suggests that metabolic reprogramming is strongly associated with the progression of Alzheimer disease and may contribute to its pathophysiology, representing a promising therapeutic axis.</p>