Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6810876 | Neurobiology of Aging | 2008 | 15 Pages |
Abstract
N-terminal-truncated forms of amyloid-β (Aβ) peptide have been recently suggested to play a pivotal role early in Alzheimer's disease (AD). Among them, Aβ3(pE)-42 peptide, starting with pyroglutamyl at residue Glu-3, is considered as the predominant Aβ species in AD plaques and pre-amyloid lesions. Its abundance is reported to be directly proportional to the severity of the clinical phenotype. The present study investigates the effects of soluble oligomeric Aβ3(pE)-42 after intracerebroventricular injection on mice learning ability and the molecular mechanisms of its in vitro neurotoxicity. Mice injected with soluble Aβ3(pE)-42 or Aβ(l-42) displayed impaired spatial working memory and delayed memory acquisition in Y-maze and Morris water maze tests, while those injected with soluble Aβ(42-1) showed no effect. These cognitive alterations were associated with free radical overproduction in the hippocampus and olfactory bulbs, but not in the cerebral cortex or cerebellum. In vitro, Aβ3(pE)-42 oligomers induced a redox-sensitive neuronal apoptosis involving caspase activation and an arachidonic acid-dependent pro-inflammatory pathway. These data suggest that Aβ3(pE)-42 could mediate the neurodegenerative process and subsequent cognitive alteration occurring in preclinical AD stages.
Keywords
PBSDMEMMAFPAβDAPIICVintracerebroventricularcPLA23-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide4,6-diamidino-2-phenylindoleDulbecco's modified Eagle's mediumMTTNeuronal apoptosisAlzheimer's diseasemethyl arachidonyl fluorophosphonatePhosphate-buffered salineamyloid-β peptideLearning and memory
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Ihsen Youssef, Sabrina Florent-Béchard, Catherine Malaplate-Armand, Violette Koziel, Bernard Bihain, Jean-Luc Olivier, Brigitte Leininger-Muller, Badreddine Kriem, Thierry Oster, Thierry Pillot,