Label-free distribution of anti-amyloid D-AIP in Drosophila melanogaster: prevention of Aβ42-induced toxicity without side effects in transgenic flies.

Authors:
Yifei Zhong
Yifei Zhong
Longhua Hospital
China
Dr Adeola Shobo, PhD
Dr Adeola Shobo, PhD
McGill University
Dr
Montreal , McGill University | Canada
Mark A Hancock
Mark A Hancock
McGill University
Montréal | Canada
Gerhard Multhaup
Gerhard Multhaup
McGill University Montreal
Germany

J Neurochem 2019 May 11. Epub 2019 May 11.

Department of Pharmacology & Therapeutics, Life Sciences Complex, McGill University, Montreal, QC, Canada.

Soluble oligomers of the 42-amino acid amyloid beta (Aβ42) peptide are highly toxic and suspected as the causative agent of synaptic dysfunction and neuronal loss in Alzheimer's disease (AD). Previously, we have shown that a small, D-amino acid Aβ42-oligomer interacting peptide (D-AIP) can neutralize human Aβ42-mediated toxicity using in vitro and cell-based assays. In the present longitudinal study using a transgenic Drosophila melanogaster model, advanced live confocal imaging and mass spectrometry imaging (MALDI-MSI) showed that the eight amino acid D-AIP can attenuate Aβ42-induced toxicity in vivo. By separating male and female flies into distinct groups, the resultant distribution of ingested D-AIP was different between the sexes. The Aβ42-induced 'rough eye' phenotype could be rescued in the female transgenics, likely because of the co-localization of D-AIP with human Aβ42 in the female fly heads. Interestingly, the phenotype could not be rescued in the male transgenics, likely because of the co-localization of D-AIP with a confounding male-specific sex peptide (Acp70A candidate in MSI spectra) in the gut of the male flies. As a novel, more cost-effective strategy to prevent toxic amyloid formation during the early stages of AD (i.e. neutralization of toxic low-order Aβ42 oligomers without creating larger aggregates in the process), our longitudinal study establishes that D-AIP is a stable and highly effective neutralizer of toxic Aβ42 peptides in vivo.

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http://dx.doi.org/10.1111/jnc.14720DOI Listing
May 2019
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