| First Author | Yin JX | Year | 2016 |
| Journal | Neurobiol Aging | Volume | 39 |
| Pages | 25-37 | PubMed ID | 26923399 |
| Mgi Jnum | J:234509 | Mgi Id | MGI:5790145 |
| Doi | 10.1016/j.neurobiolaging.2015.11.018 | Citation | Yin JX, et al. (2016) Ketones block amyloid entry and improve cognition in an Alzheimer's model. Neurobiol Aging 39:25-37 |
| abstractText | Sporadic Alzheimer's disease (AD) is responsible for 60%-80% of dementia cases, and the most opportune time for preventive intervention is in the earliest stage of its preclinical phase. As traditional mitochondrial energy substrates, ketone bodies (ketones, for short), beta-hydroxybutyrate, and acetoacetate, have been reported to provide symptomatic improvement and disease-modifying activity in epilepsy and neurodegenerative disorders. Recently, ketones are thought as more than just metabolites and also as endogenous factors protecting against AD. In this study, we discovered a novel neuroprotective mechanism of ketones in which they blocked amyloid-beta 42, a pathologic hallmark protein of AD, entry into neurons. The suppression of intracellular amyloid-beta 42 accumulation rescued mitochondrial complex I activity, reduced oxidative stress, and improved synaptic plasticity. Most importantly, we show that peripheral administration of ketones significantly reduced amyloid burden and greatly improved learning and memory ability in a symptomatic mouse model of AD. These observations provide us insights to understand and to establish a novel therapeutic use of ketones in AD prevention. |
