# Shared risk and pathology in Alzheimer's disease and glaucoma

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $181,533

## Abstract

Project Summary:
Alzheimer’s disease (AD) and glaucoma are two of the most prevalent age-related neurodegenerative disorders
recognized worldwide. Globally, AD is the most widespread cause of dementia and a substantial cause of death,
while glaucoma is the leading cause of irreversible blindness. In glaucoma, a characteristic optic neuropathy is
associated with progressive visual field defects. AD patients are 2-3 times more likely to develop glaucoma than
those without AD and epidemiologic studies have also identified increased risk for glaucoma patients to develop
AD. Histopathological hallmarks of AD in the brain, including amyloid beta (Aβ) accumulation and plaque
formation; increase in hyperphosphorylated microtubule associated tau (pTau) protein and its somatodendritic
mislocalization; microgliosis with microglial activation, and neuronal degeneration, have also been identified in
the retina and optic nerve in AD and in glaucoma supporting observed disease associations. There is currently
no cure for either disease, although treatments that lower intraocular pressure (IOP) can slow progression of
vision loss glaucoma. An association between AT1 receptor blocker (ARB) therapy and reduction in AD
neuropathology has been documented in a large, multi-center brain autopsy series. However, it is challenging to
evaluate drug effects and tease apart shared risk for glaucoma and AD in older human populations with other
age-associated co-morbidities. We will leverage data and tissues from our ongoing studies of mechanisms
underlying optic nerve head gliosis and their response to ARB therapy in a translationally relevant large-animal
glaucoma model to interrogate associations between ARB therapy, IOP, TGFβ, and AD-like neuropathology in
glaucoma. To test the hypothesis that ARB therapy will reduce AD-like pathology in glaucoma, we will conduct
a systematic evaluation of histologic markers in ARB- and placebo-treated cats with glaucoma, with wt controls.
Studies will include quantification of relevant cells, proteins and transcripts, such amyloid beta (Aβ),
hyperphosphorylated tau (pTau) protein and microglial markers, and neuronal degeneration in retina, optic nerve
and selected brain regions, in age-matched, placebo- and telmisartan- treated animals with spontaneous
glaucoma. Success in these studies will provide mechanistic insight into glaucoma risk in AD patients and will
provide a scientific foundation for future studies to develop new therapeutic strategies to slow disease
progression and enhance quality of life in AD and glaucoma patients. By leveraging precious tissue resources
generated by our current R01-funded project, we will generate preliminary data as a foundation for the design of
longer-term mechanistic studies in which we plan to address our broader hypotheses, linking AD and glaucoma
using complementary models. More specifically, results obtained in experiments funded by this administrative
supplement are likely to enhance understan...

## Key facts

- **NIH application ID:** 10123592
- **Project number:** 3R01EY027396-04S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Gillian Jane McLellan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $181,533
- **Award type:** 3
- **Project period:** 2017-09-30 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123592

## Citation

> US National Institutes of Health, RePORTER application 10123592, Shared risk and pathology in Alzheimer's disease and glaucoma (3R01EY027396-04S1). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10123592. Licensed CC0.

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