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

Guerreiro et al, Cell 2013

How geneticists think about disease Guerreiro et al, Cell 2013

Rest of the talk Why is AD genetics important?

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

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

10 years is a long, long time

Riboflavin pathway in Brown-Vialetto-Van Laere Syndrome

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

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

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

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

How else might genetics help? Disease prediction

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

Genetics plays a key role in all parts of the circle

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!!!