| First Author | Nagarathinam A | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 49 | Pages | 19284-94 |
| PubMed ID | 24305824 | Mgi Jnum | J:204148 |
| Mgi Id | MGI:5529722 | Doi | 10.1523/JNEUROSCI.2542-13.2013 |
| Citation | Nagarathinam A, et al. (2013) Membrane-anchored Abeta accelerates amyloid formation and exacerbates amyloid-associated toxicity in mice. J Neurosci 33(49):19284-94 |
| abstractText | Pathological, genetic, and biochemical hallmarks of Alzheimer's disease (AD) are linked to amyloid-beta (Abeta) peptide aggregation. Especially misfolded Abeta42 peptide is sufficient to promote amyloid plaque formation. However, the cellular compartment facilitating the conversion of monomeric Abeta to aggregated toxic Abeta species remains unknown. In vitro models suggest lipid membranes to be the driving force of Abeta conversion. To this end, we generated two novel mouse models, expressing either membrane-anchored or nonanchored versions of the human Abeta42 peptide. Strikingly, membrane-anchored Abeta42 robustly accelerated Abeta deposition and exacerbated amyloid-associated toxicity upon crossing with Abeta precursor protein transgenic mice. These in vivo findings support the hypothesis that Abeta-membrane interactions play a pivotal role in early-onset AD as well as neuronal damage and provide evidence to study Abeta-membrane interactions as therapeutic targets. |
