The document summarizes research using Drosophila melanogaster (fruit flies) as a model system to study Alzheimer's disease. Expressing human amyloid beta 42 (Aβ42) and amyloid precursor protein C99 proteins in fruit flies results in decreased survival rates, with Aβ42 expression significantly lowering survival earlier. Behavioral assays also showed learning defects in flies expressing Aβ42. The research aims to further study the effects of different Alzheimer's disease-related proteins in flies and investigate ways to modify expression levels and environmental conditions to better model aspects of the human disease.

1. Alzheimer ’s in Fruit Flies: Testing a Model System Justin de Lannoy & Shannon Harringer Cathy McElwain Loyola Marymount University, Biology Department LMU SURP

2. Alzheimer’s pathology Fig.1 Structural magnetic resonance imaging (MRI). Image of patient ’s brain with severe Alzheimer’s disease (bottom) and age-matched control (top). Atrophy of the hippocampus and cortex can be observed. Adapted from Minati et al. (2009). Introduction

3. AB42 plaque Fig. 3 Neutric plaque comprised of A  42 found in hippocampus of Alzheimer ’s patient. Adapted from Wang et al. (2000). Introduction

4. Alzheimer’s Protein Fig. 2 The amyloid precursor protein (APP) is processed in two distinct pathways, the α pathway and the β pathway. The β pathway yields 3 products, APP-β, the Aβ42/Aβ40 product and the C-terminal 99 amino acid fragment C99). (after Puglielli, 2002). Introduction

5. Alzheimer’s in Drosophila Introduction http://marvellousmenagerie.wordpress.com/

6. Expressing Alzheimer’s proteins in Drosophila melanogaster Fig. 4 Actin drives the production of the GAL4 which activates the UAS element. This activation causes the expression of the C99 protein. Introduction

7. Introduction Introduction

8. Determining Survival Rate Methods

9. Survival Rates – Spring 2011 Fig. 6. A comparison of Finelli et al. with the McElwain Lab. The percent survival was recorded for each day for each line, Aβ42 (Red) and C99 (Blue). The expression of the Aβ42 peptide results in lower survival beginning as early as 10-12 days after emergence. All Aβ42 flies die before day 27. There are still survivors in the C99 line as late as 33 days. This difference is significant (p=.002). Results

12. Summer Survival Rates Results

13. Spring and Summer Survival Rates Results

14. Survival Rates – Spring 2011 Fig. 6. A comparison of Finelli et al. with the McElwain Lab. The percent survival was recorded for each day for each line, Aβ42 (Red) and C99 (Blue). The expression of the Aβ42 peptide results in lower survival beginning as early as 10-12 days after emergence. All Aβ42 flies die before day 27. There are still survivors in the C99 line as late as 33 days. This difference is significant (p=.002). Results

19. Questions?