Understanding the genetic mechanism of Alzheimer's Disease

The purpose of our study is to identify effective therapeutic targets for Alzheimer’s disease (AD) through stratifying this heterogeneous disorder into subtypes. We will (i) define specific patient segments based on known genetic risks such as ApoE genotype and AD-related phenotypes, and (ii) identify novel genetic factors and understand the biological and pathological mechanism for the specific segment.
The specific patient segments will be defined and characterized by the known genetic risks such as ApoE genotype, and AD-related phenotypes, including symptoms, clinical progression, brain imaging and Braak stages. The whole genome sequencing data and the whole exome sequencing data will be analyzed to identify novel genetic variants or genes associated in case-control cohort for each specific segment. These findings will be confirmed with family-based association analyses.
We plan to analyze the whole genome sequencing data and the whole exome sequencing data with several phenotype-variant analysis approaches. First, we will stratify and characterize the patients by the known genetic risks and AD-related phenotypes, including symptoms, clinical progression, brain imaging and Braak stages. Then, we will analyze common variants, rare variants, including loss of function mutation, to identify novel genetic variants associated to each specific segment. These findings will be confirmed with family-based association analyses. System biological approaches will be used to determine perturbation of specific genes or pathways related to the phenotypes and to understand the molecular mechanism in each segment by integrating public data such as gene expression data that could be useful to identify the relevant brain region and cell types.
All data will remain anonymized and securely stored, and only those listed on our application and their staff will have access to these data. We will not share any of the individual level data outside of Sumitomo Dainippon Pharma nor beyond the researchers on our application. We will adhere to all agreements through the DSS NIAGADS. We have a secure computational environment where we will use these data.

The purpose of our study is to identify effective therapeutic targets for Alzheimer’s disease. Alzheimer’s disease is heterogeneous disease, which result from different combinations of genetic factors as well as environmental factors. Stratifying this heterogeneous disorder into subtypes based on genetic factors and objective phenotypes is important step to discover effective therapeutic targets. The whole genome sequencing data and the whole exome sequencing data will be analyzed to identify novel genetic variants associated with disease and/or subtypes.