# Genetic Modifiers of Protein Interaction Networks in Tauopathy

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $663,204

## Abstract

The goal of this proposal is to determine how ApoE polymorphisms modify comprehensive
maps and subnetworks of protein complexes that are central players in the dysfunction
occurring Alzheimer’s disease (AD). We will use the emerging power of quantitative network
proteomics in the Emili laboratory combined with proximity profiling to systematically
characterize the major protein assemblies that occur in a classic disease model of tauopathy.
This research will be propelled by discoveries from the Wolozin laboratory demonstrating
that a dynamic network of protein interactions drives tau biology and changes with the
course of disease. The work will be further informed by cross-referencing key network members
to large genetics and genomics datasets focused on AD risk, neuropathological outcomes
and human brain expression data to enable prioritization of network members exhibiting
disease-linked gene-gene interactions. These advanced interactome screening technologies
are uniquely suited for unbiased interrogations of disease-related protein networks in the
brain. We hypothesize that tau and RNA binding protein interactomes exhibit a progressive
evolution with disease progression in tauopathy, and that the structure of the interactomes is
modified by genetic risk factors for AD. Aim 1 will determine how APOE alleles modify
neuronal interactomes with disease progression. We will cross PS19 P301S tau mice with mice
carrying humanized ApoE3 or ApoE4, and compare protein-protein interaction networks for
tau and the RNA binding proteins TIA1 (which interacts with pathological tau) and G3BP
(which does not interact with pathological tau). Aim 2 will determine how APOE alleles
modify responses to propagated pathological tau. We will compare how propagation of
different tau strains changes the proteins that interact with pathological tau, and how
expression of specific ApoE isoforms modify the pattern of tau propagation and the nature of
the resulting tau interactomes. Aim 3 will determine how reduction of key protein interactors
modifies AD-related networks, and disease progression in tauopathy. This work will examine
the how reducing key network components modifies related interactome networks and
disease progression in PS19xApoE3 or E4 mice under conditions of normal disease
progression or accelerated progression induced by tau propagation.

## Key facts

- **NIH application ID:** 10126792
- **Project number:** 5R01AG064932-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Andrew EMILI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $663,204
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126792

## Citation

> US National Institutes of Health, RePORTER application 10126792, Genetic Modifiers of Protein Interaction Networks in Tauopathy (5R01AG064932-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10126792. Licensed CC0.

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