Affiliations: [a] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA
| [b] Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
| [c] Johns Hopkins Drug Discovery, Johns Hopkins University, Baltimore, MD, USA
Correspondence:
[*]
Correspondence to: Dr. Adam Kaplin, Johns Hopkins University School of Medicine, Meyer 121, 600N. Wolfe St., Baltimore, MD 21287, USA. Tel.: +1 410 929 5544; E-mail: akaplin@jhmi.edu and Dr. Barbara Slusher, Johns Hopkins University School of Medicine, Rangos Suite 277, 855N. Wolfe St., Baltimore, MD 21205, USA. Tel.: +1 410 614 0662; bslusher@jhmi.edu.
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
