β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

This study identifies beta-hydroxybutyrate as a regulator of protein solubility. The authors report that beta-hydroxybutyrate-induced protein insolubility does not depend on covalent protein modification, pH or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. The mechanism is selective for pathological proteins such as amyloid-beta, and exogenous beta-hydroxybutyrate ameliorated pathology in nematode models of amyloid-beta aggregation toxicity. Mass spectrometry proteomics showed enrichment of neurodegeneration-related proteins among targets and their clearance from mouse brain.