RT Journal Article
SR Electronic
T1 Membrane-Anchored Aβ Accelerates Amyloid Formation and Exacerbates Amyloid-Associated Toxicity in Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 19284
OP 19294
DO 10.1523/JNEUROSCI.2542-13.2013
VO 33
IS 49
A1 Amudha Nagarathinam
A1 Philip Höflinger
A1 Anika Bühler
A1 Claudia Schäfer
A1 Gillian McGovern
A1 Martin Jeffrey
A1 Matthias Staufenbiel
A1 Mathias Jucker
A1 Frank Baumann
YR 2013
UL http://www.jneurosci.org/content/33/49/19284.abstract
AB Pathological, genetic, and biochemical hallmarks of Alzheimer's disease (AD) are linked to amyloid-β (Aβ) peptide aggregation. Especially misfolded Aβ42 peptide is sufficient to promote amyloid plaque formation. However, the cellular compartment facilitating the conversion of monomeric Aβ to aggregated toxic Aβ species remains unknown. In vitro models suggest lipid membranes to be the driving force of Aβ conversion. To this end, we generated two novel mouse models, expressing either membrane-anchored or nonanchored versions of the human Aβ42 peptide. Strikingly, membrane-anchored Aβ42 robustly accelerated Aβ deposition and exacerbated amyloid-associated toxicity upon crossing with Aβ precursor protein transgenic mice. These in vivo findings support the hypothesis that Aβ–membrane interactions play a pivotal role in early-onset AD as well as neuronal damage and provide evidence to study Aβ–membrane interactions as therapeutic targets.