1. What we are learning about Alzheimer’s disease genetics Bryan J. Traynor

2. Guerreiro et al, Cell 2013

3. How geneticists think about disease Guerreiro et al, Cell 2013

4. Rest of the talk Why is AD genetics important?

5. Why find genes? Clinical – Diagnosis of patients – Genetic counseling

6. Genes are the starting point Clinical – Diagnosis of patients – Genetic counseling Scientific – Cell-based and animal based models – Understand the pathogenesis of disease – Provide therapeutic targets

7. 10 years is a long, long time

8. Riboflavin pathway in Brown-Vialetto-Van Laere Syndrome

9. Identify the locus Find the gene Identify a target Treatment Understand the pathobiology How else might genetics help?

10. Identify the locus Find the gene Identify a target Treatment Understand the pathobiology How else might genetics help?

11. Dementia is not one disease Important for clinical trials – What if a DMD only works on one type? – Select patients based on genetic makeup – Stratify the results based on genotype

12. How else might genetics help? What if genetics also predicts rate of progression?

13. How else might genetics help? Disease prediction

14. Parkinson’s disease 13,708 cases and 95,282 controls Nalls et al, Nature Genetics 2014

15. Genetics plays a key role in all parts of the circle

16. What are the challenges Resources are limited From a genetic perspective, disease is complex Recognize that strength lies in integrated studies, but we still need to maintain own identities Many approaches, all valid, all expensive!!!