The NAAG'ing Concerns of Modeling Human Alzheimer's Disease in Mice

Kristen R. Hollinger; Jesse Alt; Rana Rais; Adam I. Kaplin; Barbara S. Slusher

doi:10.3233/JAD-181251

The NAAG'ing Concerns of Modeling Human Alzheimer's Disease in Mice

Kristen R. Hollinger, Jesse Alt, Rana Rais, Adam I. Kaplin, Barbara S. Slusher

School of Medicine

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Studies over the past two decades report significant reductions in brain N-acetylaspartyl glutamate (NAAG) levels in neurodegenerative diseases with associated cognitive impairment, including Alzheimer's disease (AD). Because NAAG is cleaved by glutamate carboxypeptidase II (GCPII), restoration of brain NAAG levels via GCPII inhibition is a potential therapeutic strategy for AD. Herein, studies were conducted to identify an appropriate murine model of AD that recapitulates human brain NAAG changes in order to preclinically evaluate the therapeutic benefit of GCPII inhibition. Our opposing findings of brain NAAG changes in human and mouse AD highlights the limited predictive value of AD mouse models.

Original language	English (US)
Pages (from-to)	939-945
Number of pages	7
Journal	Journal of Alzheimer's Disease
Volume	68
Issue number	3
DOIs	https://doi.org/10.3233/JAD-181251
State	Published - 2019

Keywords

Alzheimer's disease
animal models
drug discovery
mass spectrometry

ASJC Scopus subject areas

General Neuroscience
Clinical Psychology
Geriatrics and Gerontology
Psychiatry and Mental health

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10.3233/JAD-181251

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abstract = "Studies over the past two decades report significant reductions in brain N-acetylaspartyl glutamate (NAAG) levels in neurodegenerative diseases with associated cognitive impairment, including Alzheimer's disease (AD). Because NAAG is cleaved by glutamate carboxypeptidase II (GCPII), restoration of brain NAAG levels via GCPII inhibition is a potential therapeutic strategy for AD. Herein, studies were conducted to identify an appropriate murine model of AD that recapitulates human brain NAAG changes in order to preclinically evaluate the therapeutic benefit of GCPII inhibition. Our opposing findings of brain NAAG changes in human and mouse AD highlights the limited predictive value of AD mouse models.",

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AU - Slusher, Barbara S.

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The NAAG'ing Concerns of Modeling Human Alzheimer's Disease in Mice

Abstract

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