Fructose-bisphosphate aldolase A

Fructose-bisphosphate aldolase A (ALDOA) is a glycolytic enzyme that catalyzes the reversible conversion of fructose 1,6-bisphosphate into two triose phosphates, playing a central role in glycolysis and gluconeogenesis (UniProt: P04075). The protein may also function as a scaffolding molecule. ALDOA is associated with glycogen storage disease 12 (GSD12), a rare metabolic disorder characterized by hepatic glycogen accumulation and hemolytic anemia that can progress to exercise-intolerant myopathy and rhabdomyolysis.

In Alzheimer's Disease, ALDOA is downregulated in post-mortem brain tissue from AD patients compared to age-matched controls, with a mean log2 fold-change of −0.43 across subcellular fractions (Chaparral AD proteomics). This reduction suggests impaired glycolytic capacity in the AD brain, consistent with metabolic dysfunction documented in neurodegeneration. The downregulation was detected via quantitative proteomics (TMT-labeled, data-dependent acquisition) across multiple subcellular fractions, indicating a broad reduction rather than compartment-specific changes.