Title

Ketones Block Amyloid Entry and Improve Cognition in an Alzheimer's Model

Department

neurology

Document Type

Article

Abstract

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-β 42, a pathologic hallmark protein of AD, entry into neurons. The suppression of intracellular amyloid-β 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.

Medical Subject Headings

neurology

Publication Date

2016

Publication Title

Neurobiology of Aging

ISSN

0197-4580

Volume

39

First Page

25

Last Page

37

Digital Object Identifier (DOI)

10.1016/j.neurobiolaging.2015.11.018

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