Recent evidence suggests that the presence of anxiety and depression, or elevated cortisol, at the earliest stages of Alzheimer’s disease (AD) predict accelerated disease progression. While the negative consequences of high levels of cortisol on neuronal function and survival have been understood for many years, little is known about why this system becomes over-active in AD or in other neurodegenerative diseases. We aim delineate the mechanisms of stress pathway disruption in AD. This will provide important clues on how stress biology interacts with neurodegenerative disease to produce neuropsychiatric co-morbidities such as late-life depression, increased anxiety and even PTSD. Our long term goal is to demonstrate that pharmacologically targeting the CRF system is a viable option to treat anxiety-related features of neurodegenerative disease and to potentially limit the progression of these debilitating diseases.

Nicholas Justice obtained a B.A. from the University of California at Berkeley, with a major in Molecular and Cellular Biology and a minor in Philosophy. He completed honor’s thesis undergraduate work with John Ngai studying the olfactory system in zebrafish. Moving across the bay to San Francisco, he completed his graduate studies in Neuroscience at the University of California, San Francisco (UCSF). He studied in the lab of Yuh Nung Jan where he wrote his Ph.D. dissertation on mechanisms of neural cell fate specification in Drosophila melanogaster. For post-doctoral training, Nick moved to the Salk Institute in San Diego, where he studied under Wylie Vale and learned the intricacies of how the body responds to stress. He then moved to Houston as an Instructor at Baylor College of Medicine studying stress in Alzheimer’s Disease, before accepting a faculty position at IMM.


  • Mechanisms of CRF system perturbation in Alzheimer’s Disease
  • In vitro characterization of CRF neurons response to toxic amyloid species
  • Characterization of CRF system specific mis-expression of mutant APP proteins    in mice
  • Tracing of CRF circuitry in AD model animals
  • The coincidence of PTSD and Alzheimer’s Disease
  • Why are AD model animals more sensitive to PTSD-like induction?
  • How does PTSD-like induction impact AD progression?
  • Defining neuronal circuits that respond to stress
  • Optogenetic manipulation of central autonomic circuitry – impact on endocrine and behavioral responses
  • Optogenetic characterization of a new local circuit that controls HPA axis activity
  • Tracing circuit connections within the Central Autonomic system


Research articles, reviews and book chapters:

  1. Rissman RA, Staup MA Lee AR , Justice NJ, Rice KC, Vale W, Sawchenko PE. Corticotropin-Releasing Factor Receptor-Dependent Effects of Repeated Stress on Tau Phosphorylation, Solubility and Aggregation. Proc Natl Acad Sci, 2012, Apr 17;109(16):6277-82.
  2. Guo Q, Zheng H, Justice NJ*. Central CRF system perturbation in an Alzheimer’s disease knockin mouse model. Neurobiol Aging. 2012, Nov; 33(11):2678-91. (*Corresponding Author)
  3. Guo Q, Li H, Gaddam SS, Justice NJ, Robertson CS, Zheng H. Amyloid precursor protein revisited: neuron-specific expression and highly stable nature of soluble derivatives. J Biol Chem. 2012 Jan 20;287(4):2437-45.
  4. Justice NJ, Blount AL, Pelosi E, Vale W, Bilezikjian LM. Impaired FSHβ expression in Foxl2 Mutant Pituitaries, Mol Endocrinol. 2011 Aug;25(8):1404-15.
  5. Sztainberg, Y, Kuperman, Justice NJ, Chen, A. An anxiolytic role for CRF receptor type 1 in the globus pallidus. J Neurosci. 2011 Nov 30;31(48):17416-24.
  6. Yang L, Wang Z, Wang B, Justice NJ, Zheng H. 2009. Amyloid precursor protein regulates Cav1.2 L-type calcium channel levels and function to influence GABAergic short-term plasticity. J. Neurosci. 29(50):15660-8.
  7. Blount AL, Schmidt K, Justice NJ, Vale WW, Fischer WH, Bilezikjian LM. “FoxL2 and Smad3 coordinately regulate follistatin gene transcription.” J Biol Chem. 2009 Mar 20;284(12):7631-45.
  8. Justice NJ, Yuan ZF, Sawchenko PE, and Vale W. “Reconciling Ligand-Receptor Misalignment in the Central CRF System:  Insights from a Transgenic Mouse Line Reporting Type 1 Corticotropin-Releasing Factor Receptor Expression.” J. Comp. Neurol 2008 Dec 1;511(4):479-96.
  9. Justice NJ and Lee KF. “Corticotropin Releasing Factor Receptor Deficiency in Mice.” Encyclopedia of Stress. Ed. George Fink. 4 vols. Academic Press, 2007. 623-626.
  10. Justice N, Roegiers F, Jan LY and Jan YN. (2003) “Lethal giant larvae acts together with numb in Notch inhibition and cell fate specification in the Drosophila adult sensory organ precursor lineage.” Curr. Biol. 13(9):778-83.
  11. Justice NJ and Jan YN. (2003) “A lethal giant kinase in cell polarity.” Nat Cell Biol. 5(4):273-4.
  12. Justice NJ and Jan YN. (2002) “Variations on the Notch pathway in neural development.” Curr Opin Neurobiol. 12(1):64-70.
  13. Barth AL, Justice NJ and Ngai J. (1996) “Asynchronous onset of odorant receptor expression in the developing zebrafish olfactory system.” Neuron. 16(1):23-34.