Patrick Sullivan, PhD

Associate Professor of Medicine
Campus mail 508 Fulton St., Grecc 182, Durham, NC 27705
Phone (919) 286-0411
Email address p.sullivan@duke.edu

The primary focus of my lab is to investigate the relationship between APOE genotype and late onset Alzheimer’s disease (AD).  The single most common and influential gene in AD is the APOE gene.  The APOE gene is polymorphic; encoding three different alleles designated APOE2, E3 or E4.  APOE4 carriers have the highest risk for AD while APOE3 carriers have an essentially neutral risk and APOE2 carriers may be protected against AD.  The APOE4 gene is also linked to increased risk for atherosclerosis, cerebral amyloid angiopathy, peripheral neuropathy, multiple sclerosis, stroke and type II diabetes; as well as an increased susceptibility to HIV and Chlamydia infections, head injury and cognitive decline following coronary bypass surgery.  The fact that 28% of the US population are carriers of the APOE4 gene, underscores the need for a better understanding of APOE’s relationship to disease.  The major challenge facing researchers today is determining why some APOE4 carriers succumb to disease while others do not.  Genetic modifiers and environmental risk factors likely explain different individual outcomes. The primary environmental risk factors are thought to be; a Westernized diet, low physical activity, chronic stress, poor sleep habits, andro/menopause and most importantly, age.

We are currently working to test novel drug formulations that specifically target putative apoE dependent mechanisms involved in neurodegeneration.  Our initial screens involve neuronal-glial cell culture models that eventually will lead to testing in animals.  We currently use the best available animal model of apoE-linked AD, the human apoE targeted replacement (TR) or “knock in” mice.  I created three lines of human apoE TR mice, each expressing one the three human apoE isoforms and have since made multiple crosses to other AD related genes (e.g. APP, PS1 and tau).  I have given the apoE TR mice and made the crosses available to over 70 labs worldwide.

We are also working to build a better model of late onset AD by combining the apoE TR mice with non-mutated human APP and tau KI mice.  We think this is important because over 98% of all AD cases contain no mutations in the APP or tau genes.  Our hope is to better understand the true etiology and progression of late onset AD.  If successful this new model should aid in both novel target identification and new drug testing to produce therapeutics with greater efficacy in treating AD.

Education and Training

  • Ph.D., University of North Carolina at Chapel Hill, 1993

Publications

Peterson, Matthew J., Dana K. Thompson, Carl F. Pieper, Miriam C. Morey, Virginia B. Kraus, William E. Kraus, Patrick Sullivan, Gerda Fillenbaum, and Harvey J. Cohen. “A Novel Analytic Technique to Measure Associations Between Circulating Biomarkers and Physical Performance Across the Adult Life Span..” J Gerontol a Biol Sci Med Sci 71, no. 2 (February 2016): 196–202. https://doi.org/10.1093/gerona/glv007.

PMID
25745025
Full Text

Cacciottolo, Mafalda, Amy Christensen, Alexandra Moser, Jiahui Liu, Christian J. Pike, Conor Smith, Mary Jo LaDu, et al. “The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice..” Neurobiol Aging 37 (January 2016): 47–57. https://doi.org/10.1016/j.neurobiolaging.2015.10.010.

PMID
26686669
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Liao, Fan, Tony J. Zhang, Hong Jiang, Katheryn B. Lefton, Grace O. Robinson, Robert Vassar, Patrick M. Sullivan, and David M. Holtzman. “Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models..” Acta Neuropathologica Communications 3 (November 10, 2015). https://doi.org/10.1186/s40478-015-0250-y.

PMID
26556230
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Levy, Olivier, Sophie Lavalette, Shulong J. Hu, Michael Housset, William Raoul, Chiara Eandi, José-Alain Sahel, Patrick M. Sullivan, Xavier Guillonneau, and Florian Sennlaub. “APOE Isoforms Control Pathogenic Subretinal Inflammation in Age-Related Macular Degeneration..” J Neurosci 35, no. 40 (October 7, 2015): 13568–76. https://doi.org/10.1523/JNEUROSCI.2468-15.2015.

PMID
26446211
Full Text

Klein, Rebecca C., Shawn K. Acheson, Brian E. Mace, Patrick M. Sullivan, and Scott D. Moore. “Altered neurotransmission in the lateral amygdala in aged human apoE4 targeted replacement mice..” Neurobiol Aging 35, no. 9 (September 2014): 2046–52. https://doi.org/10.1016/j.neurobiolaging.2014.02.019.

PMID
24698766
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Pankiewicz, Joanna E., Maitea Guridi, Jungsu Kim, Ayodeji A. Asuni, Sandrine Sanchez, Patrick M. Sullivan, David M. Holtzman, and Martin J. Sadowski. “Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice..” Acta Neuropathologica Communications 2 (June 28, 2014). https://doi.org/10.1186/s40478-014-0075-0.

PMID
24972680
Full Text

Johnson, Lance A., Reid H. J. Olsen, Louise S. Merkens, Andrea DeBarber, Robert D. Steiner, Patrick M. Sullivan, Nobuyo Maeda, and Jacob Raber. “Apolipoprotein E-low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner..” Neurobiol Dis 64 (April 2014): 150–62. https://doi.org/10.1016/j.nbd.2013.12.016.

PMID
24412220
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Nelson, Erik R., Suzanne E. Wardell, Jeff S. Jasper, Sunghee Park, Sunil Suchindran, Matthew K. Howe, Nicole J. Carver, et al. “27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology..” Science 342, no. 6162 (November 29, 2013): 1094–98. https://doi.org/10.1126/science.1241908.

PMID
24288332
Full Text

Kuszczyk, Magdalena A., Sandrine Sanchez, Joanna Pankiewicz, Jungsu Kim, Malgorzata Duszczyk, Maitea Guridi, Ayodeji A. Asuni, Patrick M. Sullivan, David M. Holtzman, and Martin J. Sadowski. “Blocking the interaction between apolipoprotein E and Aβ reduces intraneuronal accumulation of Aβ and inhibits synaptic degeneration..” Am J Pathol 182, no. 5 (May 2013): 1750–68. https://doi.org/10.1016/j.ajpath.2013.01.034.

PMID
23499462
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Bennett, Rachel E., Thomas J. Esparza, Hal A. Lewis, Eddie Kim, Christine L. Mac Donald, Patrick M. Sullivan, and David L. Brody. “Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice..” J Neuropathol Exp Neurol 72, no. 5 (May 2013): 396–403. https://doi.org/10.1097/NEN.0b013e31828e24ab.

PMID
23584199
Full Text

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