# Mechanisms and Consequences of Tau Internalization and Aggregation in the Central Nervous System

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2021 · $127,224

## Abstract

Project Summary/Abstract
Tau-related neurodegenerative diseases represent a broad class of diseases all with underlying pathology of tau
protein aggregation 1. The spread of tau aggregation throughout the brain correlates with cognitive decline in
patients and is thought to be essential for disease progression 2. In addition to tau pathology, the ability of innate
immune cells in the brain, particularly microglia and astrocytes, to mediate neuroinflammation has been
implicated as a significant contributor to disease pathogenesis. Unfortunately, a detailed understanding of how
tau spread is achieved in the central nervous system (CNS) and how this alters cross-talk between glia and
neuronal cells is still not known. In Phase I (K99) of this grant proposal we will demystify the mechanisms that
allow tau spread and uncover how cellular identity dictates response to tau insult. Preliminary work has identified
a novel tau receptor that can mediate tau uptake and has allowed us to develop testable hypotheses about
differential tau recognition between neurons and glia. Single cell RNA-sequencing experiments will allow us to
uncover the transcriptional profiles generated under tau spread conditions and will push our understanding of
how pathology is influenced by cellular identity. Following Phase I (R00), I will expand on methodology achieved
during my mentorship and focus my research on questions related to microglial tau regulation and cellular
influences on tau’s physical state. The novel experimental methods and comprehensive analyses outlined herein
will develop our understanding of pathogenic tau regulation. Further, with this mechanistic insight we will be able
to envision novel therapeutic strategies to block tau spread and aggregation.

## Key facts

- **NIH application ID:** 10075869
- **Project number:** 5K99AG064116-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Jennifer Nicole Rauch
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $127,224
- **Award type:** 5
- **Project period:** 2020-01-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075869

## Citation

> US National Institutes of Health, RePORTER application 10075869, Mechanisms and Consequences of Tau Internalization and Aggregation in the Central Nervous System (5K99AG064116-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10075869. Licensed CC0.

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