# Pathologic tau and dendritic spine loss in Alzheimer's disease

> **NIH NIH F31** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $36,890

## Abstract

PROJECT SUMMARY/ABSTRACT
 Alzheimer’s disease (AD) is the leading cause of dementia in adults over the age of 65, and currently
affects approximately 5.8 million people in the United States. As the population ages, this number is expected to
rise to 13.8 million by the year 2050. Thus, there is a need for progress in the understanding of AD etiology, as
well as in development of effective therapeutics. AD is characterized by aggregates of amyloid-β (Aβ) and of the
microtubule-associated protein tau, and the extent of tau pathology spread throughout the brain correlates with
both synapse loss and the severity of cognitive impairment. The goal of this proposal is to test the hypothesis
that accumulation of phosphorylated tau in synaptic compartments contributes to spine loss in AD. Aim 1 will
determine if postsynaptic accumulation of phosphorylated tau precedes dendritic spine loss in AD. Aim 2 will
determine if trans-synaptic spread of pathologic tau is dependent on expression of the cellular prion protein (PrPC)
in dendritic spines. PrPC is involved in Aβ- and tau-induced deficits in synaptic plasticity, and has been explored
as an Aβ-relevant therapeutic. However, this proposal will be the first to test the ability of blocking PrPC to halt
tau hyperphosphorylation and propagation, both critical events in AD pathogenesis. These aims will be achieved
through both microscopy and biochemical approaches in a tauopathy mouse model and in neuronal culture
systems. Overall, findings from the proposed project will inform on the role of pathologic tau in dendritic spine
loss and uncover mechanisms of synaptic tau accumulation and trans-synaptic propagation.

## Key facts

- **NIH application ID:** 9989459
- **Project number:** 1F31AG067635-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Courtney Kaitlin Walker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,890
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989459

## Citation

> US National Institutes of Health, RePORTER application 9989459, Pathologic tau and dendritic spine loss in Alzheimer's disease (1F31AG067635-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989459. Licensed CC0.

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