# Genetic Profiles of the Spatiotemporal Causality of Tau and Amyloid in the Elderly Brain

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $378,000

## Abstract

Project Summary (Abstract)
 The progression phenomenon of abnormal tau and amyloid-β (Aβ) proteins along neuronal circuits is
critical to understand the foundations of Alzheimer's disease (AD) pathology. The individual risk to develop late
onset AD relates to the biological and genetic profiles that confer susceptibility for abnormal and progressive
accumulation of tau and Aβ in the brain. Recent advances in multi-modal neuroimaging and genetic biomarkers
provide new prospects to detect very early stages of AD and to study its network nature and genetic
underpinnings. However, a major research challenge in this field has been to integrate and perform
comprehensive joint analysis of neuroimaging and genetic data. Thus, there is a critical need for new strategies
to detect the spreading pathways and genetic mechanisms of tau-related and Aβ-related accumulation in the
human brain. The combination of detailed descriptions of individual neuroimaging profiles of progression and
genetic vulnerability risk will offer enhanced detectability of AD trajectories. This proposal purposes to solve
these emerging challenges by focusing on identification of in vivo spreading pathways of tau and Aβ deposits
and their genetic vulnerabilities in a longitudinal sample of elderly participants from the Harvard Aging Brain
Study (HABS). In Aim 1, we will develop customized graph theory metrics to detect progression of pathology at
the network level in cross-sectional and longitudinal PET images. In Aim2, we will focus on building individualized
staging frameworks based on progression and spreading patterns of pathology using PET imaging, and we will
correlate staging estimates with clinical and neuropsychological profiles. In Aim 3, we will characterize the
genetic brain transcriptome –assisted by the Allen Human Brain Atlas- that are associated to the HABS
neuroimaging spreading profiles. At the end of this proposal, we will be able to detect and identify the early and
in vivo molecular imaging and genetic features that confer AD susceptibility in elderly individuals.

## Key facts

- **NIH application ID:** 10390455
- **Project number:** 5R01AG061445-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jorge Sepulcre
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $378,000
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390455

## Citation

> US National Institutes of Health, RePORTER application 10390455, Genetic Profiles of the Spatiotemporal Causality of Tau and Amyloid in the Elderly Brain (5R01AG061445-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10390455. Licensed CC0.

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