# Exploring the genetic basis of AD progression

> **NIH NIH R00** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $244,070

## Abstract

PROJECT SUMMARY / ABSTRACT
Late-onset Alzheimer's disease (AD) is known to have a variable temporal course and a complex genetic basis
that likely involves hundreds of loci. However, due to the lack of computational tools that can relate longitudinal
markers of AD to genetic variation, our current knowledge about the genetic underpinnings of AD progression
is very limited. To date, most genetic studies of AD are cross-sectional, which treat diagnosis, cognitive meas-
urements, or neuroimaging biomarkers of AD as stationary. Yet, the pathophysiological process of AD is dy-
namic and progressive, and individuals advance through disease stages at variable speeds. Existing genetic
studies of longitudinal AD markers often involve only a smaller number of data points spanning a short period
of time, which do not fully characterize the disease trajectory, or employ suboptimal statistical methods when
handling serial measurements, which produces biased estimates and reduces statistical power. This project
aims to systematically investigate the genetic basis of AD progression by analyzing longitudinal structural brain
magnetic resonance imaging (MRI) scans, neuropsychological assessments and genomic data from two large-
scale independently funded studies: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Harvard
Aging Brain Study (HABS). Innovative statistical methods will be developed and implemented to integrate high-
dimensional genomic data and longitudinal markers of AD (on average ~5 time points per subject spanning 3+
years) that exhibit serial dependence within subjects, missing data points, drop-outs and irregularly spaced
measurements across subjects. This project will offer critical analysis tools to model the trajectories of cogni-
tive decline and change in AD biomarkers over time, and dissect the genetic basis of AD progression. The pro-
ject will build on Dr. Ge's strong quantitative background and prior experience in neuroimaging statistics and
imaging genetics. During the award period, Dr. Ge will receive formal training in statistical genetics and ge-
nomics, and cognitive aging and AD, which will help him develop into an independent investigator and launch a
multidisciplinary research program at the intersection of imaging sciences, genomics, statistics and Alzheimer's
research.

## Key facts

- **NIH application ID:** 10070563
- **Project number:** 5R00AG054573-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Tian Ge
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $244,070
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070563

## Citation

> US National Institutes of Health, RePORTER application 10070563, Exploring the genetic basis of AD progression (5R00AG054573-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070563. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*