Development, characterisation and application of an inducible model of Alzheimer’s Disease in the fruit fly, Drosophila melanogaster
2012
Alzheimer’s disease (AD) is the most common neurodegenerative disorder and
the most prevalent form of senile dementia, affecting more than 26 million
people worldwide. The amyloid-β42 peptide (Aβ42) has been suggested to play
a central role in the pathogenesis of AD. Although the primary etiologic
mechanism of AD is unknown, it has a clear association with age. However, is it
ageing, the slow erosion of biological function, that is the cause of AD; or is
ageing merely a measure of how long it takes to accumulate toxic levels of Aβ?
To distinguish between age-dependent and age-independent effects on the rate
and extent of AD pathogenesis, an inducible model of Aβ toxicity was developed
in the fruit fly Drosophila melanogaster. This is a model system where
expression of Aβ peptides can be induced for the first time, or turned off, at
different ages.
Induced expression of the human Arctic mutant Aβ42 peptide in Drosophila
neural tissue resulted in flies with age-dependent locomotor and
electrophysiology deficits and shortened lifespan. Conditional expression of
Arctic Aβ42 at different ages was then used to show that ageing renders flies
more vulnerable to Aβ42 toxicity. The results of this thesis also served to
highlight the technical drawbacks of the GeneSwitch system and the
complexities of measuring the effect of ageing interventions such as reduced
insulin signalling and the drug rapamycin on Aβ toxicity in Drosophila.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI