# Protein co-pathologies in Alzheimer's Disease and Related Dementias

> **NIH AG R01** · UNIVERSITY OF IOWA · 2026 · $744,346

## Abstract

Abstract
Dementia is associated with staggering economic, social, and personnel costs. Strikingly, most dementia
cases have co-pathologies beyond the dominant type. Research suggests these non-dominant protein
aggregates can impact cognition, symptoms, and progression. These findings motivate our central hypothesis
that individual pathologies uniquely contribute to the degenerative trajectory of clinical dementia.
Our long-term goal is to build a model of degenerative dementia that is inclusive of co-pathology.
Accomplishing this goal requires identifying pathologies and determining how each pathology contributes to
neurodegeneration, including synapse loss, cell loss, and clinical symptoms. To accomplish this goal, we will
first determine the relationship between pathology in cutaneous nerves and pathology in the brain of
individuals that died with dementia, including Alzheimer’s disease or related disorders. There is strong
evidence tying alpha-synuclein aggregates in peripheral nerves with Parkinson’s disease. However, it is
unknown how this clinically available biomarker relates to brain pathology in patients with dementias. In Aim 2,
we will use both unbiased stereology as well as high throughput screening methods to evaluate the
relationship between brainstem pathology and cell loss. Pathology in brainstem projection neurons such as
norepinephrine producing locus coeruleus, serotonin producing dorsal raphe, and acetylcholine producing
pedunculopontine nucleus have the potential to substantially impact the brain and its response to
pharmacological treatment. Although substantial evidence supports the premise that these regions show
pathology, few studies have compared how different pathologies impact cell morphology or death. Finally, in
Aim 3 we will directly quantify how specific pathologies impact cortical synapse loss. Synapse loss is
considered one of the strongest predictors of cognitive deficits. However, studies are not definitive on which
pathologies b

## Key facts

- **NIH application ID:** 11251994
- **Project number:** 5R01AG091184-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Georgina  Aldridge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AG
- **Fiscal year:** 2026
- **Award amount:** $744,346
- **Award type:** 5
- **Project period:** 2025-01-01T00:00:00 → 2029-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11251994

## Citation

> US National Institutes of Health, RePORTER application 11251994, Protein co-pathologies in Alzheimer's Disease and Related Dementias (5R01AG091184-02). Retrieved via AI Analytics 2026-05-20 from https://api.ai-analytics.org/grant/nih/11251994. Licensed CC0.

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