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Author Notes:

Correspondence to: Andrew A. Pieper, MD PhD, Department of Psychiatry, University of Iowa Carver College of Medicine, Pappajohn Biomedical Institute, 169 Newton Road, Iowa City, IA 52242, Andrew-Pieper@uiowa.edu.

We thank Dr. Robert Cohen for generously providing a male TgF344-AD hemizygous breeder to our laboratory for establishment of the animal colony.

Andrew Pieper is co-founder and consultant of Neuroprotective Therapeutics, and holds patents related to the P7C3 series of neuroprotective compounds.

JR Voorhees, MT Remy, CJ Cintrón-Pérez, E El Rassi, MZ Kahn, LM Dutca, TC Yin, LM McDaniel, NS Williams, and DJ Brat have no biomedical financial interests or potential conflicts of interest.


Research Funding:

This work was supported by the National Institute for Environmental Health Sciences through the University of Iowa Environmental Health Sciences Research Center (NIEHS/NIH P30 ES005605) to JRV and AAP, funds to AAP from an anonymous donor to the Mary Alice Smith Fund for Neuropsychiatry Research, funds to AAP from the Titan Neurology Research Fund, funds to AAP from the Brockman Medical Research Foundation, by Department of Veterans Affairs Merit Review 1IO1BX002444 to AAP, and by CDA number IK2 RX002003 from US Dept, of Veterans Affairs RR&D to LMD.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Psychiatry
  • Neurosciences & Neurology
  • Alzheimer's disease
  • Depression
  • Neurodegeneration
  • Neurogenesis
  • Neuroprotection
  • P7C3
  • TgF344-AD
  • A-BETA

(-)-P7C3-S243 Protects a Rat Model of Alzheimer's Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

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Journal Title:

Biological Psychiatry


Volume 84, Number 7


, Pages 488-498

Type of Work:

Article | Post-print: After Peer Review


Background: In addition to cognitive deficits, Alzheimer's disease (AD) is associated with other neuropsychiatric symptoms, including severe depression. Indeed, depression often precedes cognitive deficits in patients with AD. Unfortunately, the field has seen only minimal therapeutic advances, underscoring the critical need for new treatments. P7C3 aminopropyl carbazoles promote neuronal survival by enhancing nicotinamide adenine dinucleotide flux in injured neurons. Neuroprotection with P7C3 compounds has been demonstrated in preclinical models of neurodegeneration by virtue of promoting neuronal survival independently of early disease-specific pathology, resulting in protection from cognitive deficits and depressive-like behavior. We hypothesize that P7C3 compounds might be uniquely applicable to patients with AD, given the comorbid presentation of depression and cognitive deficits. Methods: Aging male and female wild-type and TgF344-AD rats, a well-characterized preclinical AD model, were administered (−)-P7C3-S243 daily for 9 and 18 months, beginning at 6 months of age. Behavioral phenotypes related to cognition and depression were assessed at 15 and 24 months, and brain pathology and biochemistry were assessed at 24 months. Results: (−)-P7C3-S243 safely protected aging male and female wild-type and TgF344-AD rats from cognitive deficits and depressive-like behavior. Depressive-like behavior occurred earlier than cognitive deficits in TgF344-AD rats, consistent with AD in many patients. Treatment with (−)-P7C3-S243 blocked neurodegeneration in TgF344-AD rats, without altering amyloid deposition or indicators of neuroinflammation. Conclusions: Neuronal cell death–specific treatment approaches, such as P7C3 compounds, may represent a new treatment approach for patients experiencing the combination of cognitive deficits and depression associated with AD.

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© 2017

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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