Amyloid-beta–binding alcohol dehydrogenase (ABAD (also known as HSD10))

Amyloid-beta–binding alcohol dehydrogenase (ABAD), also known as 17β-hydroxysteroid dehydrogenase type 10 or HSD10, is a mitochondrial enzyme belonging to the short-chain dehydrogenase/reductase family. It plays a critical role in cellular energy regulation and steroid metabolism within neurons. In Alzheimer’s disease, amyloid-beta peptides accumulate within mitochondria where they bind directly to ABAD. This interaction disrupts normal enzymatic function—impairing NAD binding—and triggers signaling cascades that lead to increased oxidative stress, reduced estradiol levels, neuronal apoptosis, and cognitive deficits. The pathological consequences are exacerbated by elevated expression of ABAD observed in affected brain regions. Targeting the pathological interaction between amyloid-beta and ABAD has emerged as a promising therapeutic strategy for mitigating mitochondrial dysfunction associated with Alzheimer’s disease. Experimental approaches include small-molecule inhibitors or decoy peptides designed to block this protein-protein interface; these have shown neuroprotective effects in preclinical models by restoring mitochondrial function and improving memory performance[1][3][4]. However, because ABAD is essential for normal metabolic processes—including hormone homeostasis—therapeutic interventions must be carefully evaluated for potential off-target effects on neuronal health. The “Amyloid-beta–binding alcohol dehydrogenase interaction” refers specifically to this pathogenic molecular event rather than an individual gene or receptor; thus it is best described by its canonical component “Amyloid-beta–binding alcohol dehydrogenase” (ABAD/HSD10)[5].

Other names

17β-hydroxysteroid dehydrogenase type 10HSD10ERAB (endoplasmic reticulum-associated Aβ-binding protein)Amyloid beta-peptide-binding alcohol dehydrogenase

Inhibition of the ABAD–amyloid-beta interaction prevents mitochondrial dysfunction, reduces oxidative stress, and protects neurons from amyloid-beta-induced apoptosis[1][3][4].