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

Kristen R Hollinger^1,2,3, Jesse Alt³, Rana Rais^2,3

¹Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.

|March 19, 2019

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.

Keywords:

Alzheimer’s disease animal models drug discovery mass spectrometry

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