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- Title
Membrane-Anchored Aß Accelerates Amyloid Formation and Exacerbates Amyloid-Associated Toxicity in Mice.
- Authors
Nagarathinam, Amudha; Höflinger, Philip; Bühler, Anika; Schäfer, Claudia; McGovern, Gillian; Jeffrey, Martin; Staufenbiel, Matthias; Jucker, Mathias; Baumann, Frank
- Abstract
Pathological, genetic, and biochemical hallmarks of Alzheimer's disease (AD) are linked to amyloid-ß (Aß) peptide aggregation. Especially misfolded Aß42 peptide is sufficient to promote amyloid plaque formation. However, the cellular compartment facilitating the conversion of monomeric Aß to aggregated toxic Aß species remains unknown. In vitro models suggest lipid membranes to be the driving force of Aß conversion. To this end, we generated two novel mouse models, expressing either membrane-anchored or nonanchored versions of the human Aß42 peptide. Strikingly, membrane-anchored Aß42 robustly accelerated Aß deposition and exacerbated amyloid-associated toxicity upon crossing with Aß precursor protein transgenic mice. These in vivo findings support the hypothesis that Aß-membrane interactions play a pivotal role in early-onset AD as well as neuronal damage and provide evidence to study Aß-membrane interactions as therapeutic targets.
- Subjects
ETIOLOGY of Alzheimer's disease; AMYLOID genetics; PEPTIDE synthesis; DENTAL plaque; IN vitro studies; NEUROPLASTICITY
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 49, p19281
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUR0SCI.2542-13.2013