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Alzheimer's Disease in Fruit Flies
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Alzheimer's Disease in Fruit Flies

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Justin presented this slide show on July 20, 2011, at the SURP symposium to celebrate the summer research program. The exciting slide is slide 13 that shows significant improvement in survival at the …

Justin presented this slide show on July 20, 2011, at the SURP symposium to celebrate the summer research program. The exciting slide is slide 13 that shows significant improvement in survival at the 2 week mark.

Published in Health & Medicine , Technology
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  • Let’s title each of these slides with introduction as a header. I’ve changed this one. Be sure and include some of the general introductory material ---maybe incidence of Alzheimer’s, average age of onset, some behavioral characteristics. Stuff for the audience to relate to. But don’t spend a lot of time on this part.
  • Title: Alzheimer’s plaques or Alzheimer’s tangles or AB42 plaques or AB42 tangles Be sure to tie this firmly to the slide before.
  • Title: Alzheimer’s protein or Amyloid Precurosor Protein or? Be sure to talk about the two classes of products the membrane-spanning C99 and the products of the two cleavage sites AB42 and AB 40 and the AB42 is thought to form the tangles seen in Alzheimer’s apthology
  • I thought we needed a transition slide here to move into flies Talk about the advantages of fruit flies (fast breeding, lots of genetics, small space and also talk about what kinds of symptoms (short life, low activity, memory loss)
  • Title: Expressing Alzheimer’s proteins in Drosophila melanogaster or ? This is really how to get the protein in Take time with this
  • Title: Survival Rate in Alzheimer’s flies or Published Survival Rates for AB42 flies or Connect the two concepts, the behavior (early death) and the exression of the protein

Transcript

  • 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
  • 10. Proposal of Areas to Address
    • Changing the promoter
    • Mites and bacteria
    • Environmental conditions
    • Outcross the stocks
  • 11. Humidity Control
    • Previously vials were put in incubator at 29°C without regard of humdity
    • Now vials are placed in plastic boxes with papertowels that have absorbed 10mL of water
  • 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
  • 15. Learning assay
    • Conditioning apparatus used to test learning and memory
    • Iijima observed statistical learning defects after 6-7days
    • Allows for observation Alzheimer’s sooner
  • 16. Future Directions
    • Perfect the behavior assay
    • Finish the out-crosses
    • Find the right expression of the Alzheimer ’s protein to show a good difference in survival
    • Test the Moffet peptides
  • 17. References
    • Baine M, Georgie D, Shifferraw E, Nguyen T, Nogaj L, Moffet D (2009) Inhibition of a Beta 42 Aggregation Using Peptides Selected from Combinatorial Libraries . Journal of Peptide Science 15(8): 499-503.
    • Finelli A, Kelkar A, Song H, Yang H, Konsolaki Mary (2004) A Model for Studying Alzheimer's a Beta 42-Induced Toxicity in Drosophila Melanogaster . Molecular and Cellular Neuroscience 26(3): 365-75.
    • Minati, Ludovico, Trudi Edginton, Maria Grazia Bruzzone, Giorgio Giaccone (2009) Current Concepts in Alzheimer’s Disease: A Multidisciplinary Review. American Journal of Alzheimer’s Disease & Other Dementias . 24(4): 95-121.
    • Iijima K, Chiang H-C, Hearn SA, Hakker I, Gatt A, Shenton C, Granger L, Leung A, Iijima-Ando K, Zhong Y (2008) Aβ42 Mutants with Different Aggregation Profiles Induce Distinct Pathologies in Drosphila . PLoS One 3(2): e1703.
    • Iijima K, Liu HP, Chiang AS, Hearn SA, Konsolaki M, Zong Y. (2004 ) Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease . Proc Natl Acad Sci U S A. 101(17):6623-6628.
    • Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of Aβ 42(43) and Aβ 40 in senile plaques with end-specific Aβ monoclonals: evidence that an initially deposited species is Aβ 42(43). Neuron 13:45–53.
    • Tully T, Quinn WG (1985) Classical conditioning and retention in normal and mutant Drosophila melanogastor . J Comp Physiol A . 157(2):263-77.
    • Wang, Hoau-Yan, Daniel H.S. Lee, Michael R. D’Andrea, Per A. Peterson, Richard P. Shank, Allen B. Reitz (2000) Β-Amyloid1-42 Binds to α7 Nicotinic Acetylcholine Receptor with High Affinity. The Journal of Biological Chemistry. 275(8): 5626-5632
  • 18. Acknowledgements
    • LMU SURP
    • Shelby Chun Fat, Andrew Heslin, Carol Johanson, Anthony Wavrin
    • Mary Konsolaki for providing us with the Aβ42 and C99 flies and for her helpful discussions
    • The Department of Biology and the College of Science and Engineering for continuing support.
  • 19. Questions?