Download presentation
Presentation is loading. Please wait.
1
Modifiers of Amyloid-beta Toxicity in Alzheimer’s Disease
Mayida Azhar Department of Genetics Alzheimer’s disease and Dementia, 2014
2
Is there an interaction between two pools of Aβ?
3
Secreted Aβ is toxic in Drosophila
We secrete Aβ peptides from the neurons of fly brain and study toxicity Secreted Aβ is toxic in Drosophila Ab SSP Crowther et al, 2005 Crowther et al, 2005
4
Secreted Aβ is toxic in Drosophila
Reduced Longevity Wild type Aβ expressing
5
Locomotor deficit Wild type Aβ expressing
6
Plaque like deposits in the brain
0.1 mm Stanislav Ott, 2013
7
Without SSP, Aβ is expressed in cytoplasm
Ab
8
...but Cytoplasmic Aβ is non-toxic
Wild type Aβ expressing Percent survival day
9
No plaque like deposits
Stanislav Ott, 2013 Stanislav Ott, 2013
10
What happens if we co-express these constructs?
Median Survival (days) Wild type SSP Aβ NSP Aβ NSP+ SSP Aβ Stanislav Ott, 2013 Stanislav Ott, 2013
11
Increase in plaque deposition
Stanislav Ott, 2013
12
Which pathways are facilitating this synergy?
13
An example……CG1824 siRNA % increase in median survival SSP+NSP Aβ
SSP Aβ SSP+NSP Aβ wild type % increase in median survival This is an example of how our data looks like. In the presence of a certain RNAi the flies that express secreted and non secreted abeta live much longer as compared to the ones that only express secreted abeta or wild type.
14
RNAi screen outcome 13 Genes 4 Genes
15
Conclusion There is a synergistic relationship between extracellular and Cytoplasmic Aβ Gene knockdown at interface of the cells, modifies Aβ toxcity. We are trying to replicate this effect in mammalian cells and study the pathways involved
16
Stanislav Ott, Kofan Chen, Jung Yeon, Elenora Pi & Damian Crowther
Many thanks to… Stanislav Ott, Kofan Chen, Jung Yeon, Elenora Pi & Damian Crowther
Similar presentations
