2022 Alzheimer's Association Research Grant (AARG)

A Dual-Deep Learning AI Strategy to Identify Tau-associated Genetic Variants in AD

How can advanced computing techniques help identify genetic variation associated with tau accumulation in Alzheimer’s?

Taeho Jo, Ph.D.
Indiana University
Indianapolis, IN - United States

Background

Tau is a protein that helps to maintain the structure of brain cells. In Alzheimer’s and other brain diseases, the shape of tau protein becomes modified or “misfolded,” a change that may contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage. Studies show that abnormal tau protein can move from one nerve cell to another, possibly contributing to the progression of brain changes associated with Alzheimer’s and other brain diseases. Identifying genetic changes associated with tau protein accumulation may contribute to the development of new targets for therapies or strategies for early and accurate diagnostic strategies.

Research Plan

Dr. Taeho Jo and colleagues will use an advanced computer science technique called machine learning, a form of artificial intelligence, to study genetic (DNA) variations associated with the accumulation of tau protein. First, the researchers will apply their machine learning method to whole genome sequencing studies (analyses that reveal the complete genetic make-up of an individual) from the Alzheimer’s Disease Sequencing Project (ADSP), a large collection of genetic sequencing data from individuals with Alzheimer’s funded by the National Institute of Health (NIH). Next, the team will use their machine learning method to study the levels of tau using brain scans (positron emission tomography, PET). This will allow them to identify specific brain areas and patterns of tau accumulation that are potentially important in Alzheimer's. Finally, Dr. Jo and colleagues will study biological samples (such as blood) from Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD), an ongoing private-public partnership funded by the NIH, the Alzheimer’s Association, and others, to investigate the potential role of genetic variation underlying tau accumulation in the brain and the potential overlap with genes already associated with risk of developing Alzheimer’s.

Impact

The results of this project may shed light on how genetic variation impacts the accumulation of tau in the brains of individuals with Alzheimer’s and other neurodegenerative diseases. The findings may help identify novel therapy approaches associated with the accumulation of tau protein.