# Effect of Aging on Efficacy of Alzheimer-focused Therapeutic Strategies

> **NIH NIH UH3** · J. DAVID GLADSTONE INSTITUTES · 2020 · $168,462

## Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting over 5 million people in
the U.S. No effective treatments are available to prevent, halt, or reverse the disease. Although aging is the
most important nongenetic risk factor for AD, young mice have been used for the vast majority of preclinical
studies in AD-related mouse models, mainly for practical and financial reasons. Even at young ages, these
models share several pathological features with AD. However, they clearly do not simulate the full complexity
of the human condition. We hypothesize that aged mouse models will simulate the human condition to a
greater extent than young mouse models and that assessing candidate therapies in aged mouse models will
better predict the efficacy of these therapies in later clinical trials. In this UH2/UH3 proposal, we will elucidate
the phenotypic impact of natural aging in human amyloid precursor protein (hAPP) transgenic mice from line
J20—one of the most extensively used AD-related mouse models. In addition, we will compare the efficacy of
promising candidate therapies in young and old mice from this line. While strategies targeting amyloid-β (Aβ)
have justifiably received considerable attention over the past decade, it is still unclear whether they will turn out
to be both efficacious and safe in ongoing clinical trials. We reported in well-cited publications that treatment
with the anti-epileptic drug levetiracetam and genetic reduction of tau ameliorate synaptic, network and
cognitive dysfunction in hAPP-J20 mice, and these findings have been confirmed by other groups in
independent mouse models. However, it remains to be determine whether these strategies also have
beneficial effects in aging brains that have had longer exposures to pathologically elevated levels of Aβ. We
therefore propose to investigate the efficacy of levetiracetam treatment and genetic reduction of tau in old
hAPP-J20 mice.

## Key facts

- **NIH application ID:** 9978935
- **Project number:** 5UH3NS100128-05
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Lennart Mucke
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,462
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978935

## Citation

> US National Institutes of Health, RePORTER application 9978935, Effect of Aging on Efficacy of Alzheimer-focused Therapeutic Strategies (5UH3NS100128-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9978935. Licensed CC0.

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