# Targeting age-related endosome dysfunction to treat cognitive decline and Alzheimer's disease

> **NIH NIH R21** · COLORADO STATE UNIVERSITY · 2024 · $230,344

## Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a growing
humanitarian and economic burden. Advanced age is the greatest risk factor for AD so the long-
term goal of this research is to better understand how advancing age contributes to AD
occurrence and progression. Aging and AD pathology are characterized by a decline in the
cell’s ability to eliminate damaged and pathological proteins through endosome trafficking (NOT-
21-034) which contributes to the accumulation of protein like tau within neurons and other cells
of the brain. We have identified a key protein involved in the formation of endosomes, the
vehicle for endosome trafficking, that is decreased in neurons across the lifespan and further
decreased in neurons from donors with AD. We have shown that we can restore expression of
this protein in patient-derived human neurons using adeno-associated virus (AAV) and that this
decreases intracellular tau. Based on these findings, the Specific Aims of this proposal are to: 1)
determine how increasing endosome formation decreases tau in neurons and 2) define how
increasing endosome formation influences cognition and AD pathology in transgenic and aged
wild type mice. If successful, these studies will establish decreased endosome formation as a
cause of tau pathology in AD and support the development of therapeutic strategies to enhance
endosome formation for the treatment of AD and other proteinopathies (i.e., frontotemporal
dementia, Parkinson’s disease and others).

## Key facts

- **NIH application ID:** 10807655
- **Project number:** 1R21AG085586-01
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Thomas LaRocca
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $230,344
- **Award type:** 1
- **Project period:** 2024-07-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807655

## Citation

> US National Institutes of Health, RePORTER application 10807655, Targeting age-related endosome dysfunction to treat cognitive decline and Alzheimer's disease (1R21AG085586-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10807655. Licensed CC0.

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