# Disruption of sensory pathways in dementia pathogenesis

> **NIH NIH R03** · NORTHEAST OHIO MEDICAL UNIVERSITY · 2024 · $309,960

## Abstract

PROJECT SUMMARY
While dementia is considered a disease of learning and memory, early disruptions to sensory processes such
as visual impairments are shown to occur prior to cognitive decline and increase risk for Alzheimer’s disease
(AD) diagnosis. There is a lack of essential knowledge on the role visual sensory impairment plays in onset
and progression of AD. One targeted approach to resolving this gap in knowledge requires identifying how
pathological amyloid and tau protein accumulations in the eye damage the entire primary visual circuit from retina
to brain. Understanding how and when dysfunction occurs along this primary retinal pathway may illuminate new
opportunities for early intervention in AD. The objective of this R03 proposal is to uncover novel disease
mechanisms arising from visual dysfunction that can be targeted for prevention or early dementia intervention.
The central hypothesis of this research is that presence of pathological Aβ or tau in the retina causes damaging
changes along the primary retinal pathway to primary visual cortex (V1), where disease mechanisms can then
spread via V1’s interconnections to brain regions affecting learning and memory. Preliminary research shows
that pathological amyloid and tau proteins injected in the mouse eye cause hyperactivity of neurons in V1, which
can ultimately lead to neurodegeneration. This hyperactivity may result from damage to GABA interneurons in
this region. We will use experimental models that induce amyloid and tau pathology into the visual system of
healthy mice by injecting these proteins into the a) eye or b) V1 and measuring the effects of this manipulation
on visual system circuitry in accordance with the following Specific Aims: SA1) Determine how pathological
AD proteins in the eye affect structure and function of the primary visual pathway in the brain; SA2)
Determine how pathological amyloid and tau proteins in primary visual cortex (V1) impact
interconnected brain pathways. These studies will generate important preliminary data identifying
mechanisms by which early visual system pathology may damage non-visual brain regions. This work will provide
the foundation for future research addressing a critical barrier in the field of identifying targets for intervention
that can protect both visual function and disease progression in AD.

## Key facts

- **NIH application ID:** 10888472
- **Project number:** 1R03AG087423-01
- **Recipient organization:** NORTHEAST OHIO MEDICAL UNIVERSITY
- **Principal Investigator:** Christine Marie Crish
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $309,960
- **Award type:** 1
- **Project period:** 2024-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888472

## Citation

> US National Institutes of Health, RePORTER application 10888472, Disruption of sensory pathways in dementia pathogenesis (1R03AG087423-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10888472. Licensed CC0.

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