Context:
A recent study in fruit flies tested the hypothesis that accumulation of the Alzheimer’s disease associated peptide Aβ42 disrupts sleep and increases wakefulness. We contracted the Contract Research Organization (CRO) Tracked Biotechnologies to replicate the main experiment (Figure 4, C–J) from the original study and test whether sleep fragmentation can be an early biomarker of Alzheimer's disease pathology.
Resolution criteria:
This market resolves YES if the independent replication reproduces at least 2 out of 5 sleep-related outcomes from the original study (Gerstner et al. Figure 4, C–J) with p < 0.05 in the same direction of effect (Aβ42-expressing flies showing reduced or fragmented sleep compared to controls). Resolves NO otherwise.
Detailed project description:
Project summary of original paper: In the original study, fruit flies that produced the human Aβ42 protein in all neurons slept less and showed disrupted sleep patterns compared to control flies. Sleep was measured using an automated system under normal day–night cycles, with sleep defined as at least five minutes of inactivity.
Experimental setup: The main experiment from Gerstner et al. (Figure 4, C–J) will be replicated using fruit flies that produce the human Aβ42 protein, along with control flies that do not. Each group will include 35–40 flies aged 2–3 days, as in the original study. Sleep will be measured using a TrackedFlyBox™ system that records continuous video under standard day–night light cycles. Custom software will analyze the footage to detect periods of inactivity lasting five minutes or longer, which count as sleep. From these recordings, the replication study will calculate total, daytime, and nighttime sleep, as well as how often and how long the flies sleep at night, matching the measures used in Gerstner et al.
Analysis and outcome definition: Statistical comparisons (t-tests or ANOVA) will be performed between Aβ42-expressing flies and appropriate controls, following the approach of the original study. Estimated completion within 3-4 months from initiation to final report and data delivery. Success of the replication will be defined if at least 2 of the extracted 5 criteria will be replicated showing a p < 0.05 in the performed statistical tests.
Link to original paper:
Gerstner, J. R. et al. Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila. J. Neurosci. Res. 95, 1548–1564 (2017). https://pubmed.ncbi.nlm.nih.gov/27320125/
Link to original pre-registration on ResearchHub and more detailed experimental plan:
Could poor sleep be an early indicator of Alzheimer's disease? – A replication study, ResearchHub
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