# APEX2-mediated Identification of factors involved in seeding by tau protein

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $449,333

## Abstract

Propagation of tau pathology in the manner of prions has been hypothesized to underlie the progressive
accumulation of tau aggregates in tauopathies. In experimental systems it has been easy to observe
propagation of tau aggregation from the outside to the inside of the cell, and within brain networks in transgenic
mice. However, it remains unknown whether this phenomenon is the cause of progressive neurodegeneration
in human tauopathies. We do not know the molecular mechanisms by which tau aggregates taken into a cell
can replicate unique structures. The identification of factors that are involved will help test the prion hypothesis
of progressive neurodegeneration. Furthermore, understanding these mechanisms could help with the
development of new therapies. We propose to use a newly developed tool to identify and characterize factors
that are involved in tau aggregation. Ascorbate peroxidase (APEX2)-dependent proximity labeling is an
enzymatic method for time-resolved biotinylation of proteins within a cell. We will identify peptides that have
been labeled based on affinity purification and mass spectrometry. This will let us identify factors in close
proximity to tau as the aggregation process begins, after macropinocytosis or direct delivery of aggregates to
the cell interior. We will use standard genetics to follow up hits. This work could have strong impact on our
understanding of the propagation of intracellular amyloids, and could form the basis for new therapeutic
strategies.

## Key facts

- **NIH application ID:** 9896356
- **Project number:** 1R21AG064418-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MARC I DIAMOND
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,333
- **Award type:** 1
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896356

## Citation

> US National Institutes of Health, RePORTER application 9896356, APEX2-mediated Identification of factors involved in seeding by tau protein (1R21AG064418-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9896356. Licensed CC0.

---

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