title: Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.
abstract: Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ1-42form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ1-42expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.
authors.affiliation: Internal Medicine Residency Programme, SingHealth Group, Singapore.
authors.forename: Sheng
authors.initials: S
authors.lastname: Fong
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Emelyne
authors.initials: E
authors.lastname: Teo
authors.affiliation: Science Division, Yale-NUS College, Singapore.
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Ng
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore.
authors.forename: Ce-Belle
authors.initials: CB
authors.lastname: Chen
authors.affiliation: Institute of Chemical and Bioengineering, ETH Zurich, Switzerland.
authors.forename: Lakshmi Narayanan
authors.initials: LN
authors.lastname: Lakshmanan
authors.affiliation: Science Division, Yale-NUS College, Singapore.
authors.forename: Sau Yee
authors.initials: SY
authors.lastname: Tsoi
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
authors.forename: Philip Keith
authors.initials: PK
authors.lastname: Moore
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore.
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Biochemistry, National University of Singapore, Singapore.
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
authors.affiliation: Science Division, Yale-NUS College, Singapore.|Department of Biochemistry, National University of Singapore, Singapore.
authors.forename: Jan
authors.initials: J
authors.lastname: Gruber