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Robert George Nagele, Ph.D.

photo of Robert NageleProfessor

Science Center 313A
856-566-6083
nagelero@rowan.edu

Education

Rutgers University, New Brunswick, NJ, Ph.D., 1980

Research Interests

Our research is focused on two areas. The first emerged from our recent discovery that all human blood contains thousands of autoantibodies which appear to play a role in the clearance of cell and tissue debris generated by the body on a day-to-day basis. We have further shown that this is conserved among all mammals and that ongoing disease leads to an increased production of debris from the organ/tissue affected. This surge of debris enters the blood and subsequently stimulates the immune system to selectively increase the production of autoantibodies that clear this disease-specific debris. We have used human protein microarray technology and machine learning to detect and identify disease-specific autoantibodies which can now be used as biomarkers to confirm the presence of disease. Thus far, we have thus successfully employed disease-specific autoantibodies as biomarkers to diagnose Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, first episode psychosis and early-stage breast cancer in human subjects using a single drop of blood. Diagnostic accuracies for each of these diseases exceeds 95% using our analytical strategy. This work was initially seed-funded by the Foundation Venture Capital Group of the NJ Health Foundation and led to the establishment of Durin Life Sciences, Inc., a company focused on the development of blood-based diagnostic test using autoantibodies as disease-specific biomarkers and the Luminex magnetic bead-based system as the diagnostic test platform. The first blood tests for Alzheimer’s and Parkinson’s diseases are slated for release in early 2025. New efforts are currently underway towards diagnosing the effects of concussion and traumatic brain injury, where we believe that our diagnostic strategy will be able to detect the presence of neurodegenerative changes in the brain resulting from repeated trauma. A number of patents have been filed with Rowan University.

Our second research focus is to elucidate cellular and molecular mechanisms of Alzheimer’s disease. Most recently, this work has led us to conclude that breakdown of the blood-brain barrier is a requisite early trigger for a number of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. In view of this, we are now investigating factors and conditions that lead to blood-brain barrier breakdown and are utilizing the mouse as a model system to unravel the underlying mechanisms of these diseases.

Selected Publications

(Updated October 2024)

  1. NK Acharya, HC Grossman, PM Clifford, EC Levin, KR Light, H Choi, RL Swanson II, MC Kosciuk, V Venkataraman, DJ. Libon, LD Matzel, and RG Nagele. A chronic increase in blood-brain barrier permeability facilitates intraneuronal deposition of exogenous blood-borne amyloid-beta1-42 peptide in the brain and leads to Alzheimer’s disease-relevant cognitive changes in a mouse model. J Alzheimers Dis 2024;98(1):163-186. doi: 10.3233/JAD-231028. 2024

  2. DeMarshall CA, Viviano J, Emrani S, Thayasivam U, Godsey GA, Sarkar A, Belinka B, Libon DJ, Nagele R.G., Parkinson’s Study Group and the Alzheimer’s Disease Neuroimaging Initiative. Early Detection of Alzheimer's Disease-Related Pathology Using a Multi-Disease Diagnostic Platform Employing Autoantibodies as Blood-Based Biomarkers. J Alzheimers Dis.;92(3):1077-1091. doi: 10.3233/JAD-221091. 2023 PMID: 36847005

  3. Kheirkhah R, CA DeMarshall, F Sieber, E Oh and RG Nagele. The origin and nature of the complex autoantibody profile in cerebrospinal fluid. Brain, Behavior, & Immunity - Health Volume 2, 2020, 100032. 2020

  4. Goldwaser EL, Acharya NK, Wu H, Godsey GA, Sarkar A, DeMarshall CA, Kosciuk MC and Nagele RG. Evidence that Brain-Reactive Autoantibodies Contribute to Chronic Neuronal Internalization of Exogenous Amyloid-1-42 and Key Cell Surface Proteins During Alzheimer’s Disease Pathogenesis.  Journal of Alzheimer’s Disease 74 (2020) 345–361 DOI 10.3233/JAD-190962 IOS Press 345. 2020

  5. Emrani S, Lamar M, Price CC, Wasserman V, Matusz E, Au R, Swenson R, Nagele R, Heilman KM, Libon DJ. Alzheimer’s/vascular spectrum dementia: Classification in addition to diagnosis. J Alzheimers Dis. 2020;73(1):63-71. doi: 10.3233/JAD-190654.PMID: 31815693. 2020

  6. DeMarshall C, Oh E, Kheirkhah R, Sieber F, Zetterberg H, Blennow K, Nagele RG. Detection of early-stage Alzheimer's pathology using blood-based autoantibody biomarkers in elderly hip fracture repair patients. PLoS One 14(11): e0225178. doi: 10.1371/journal.pone.0225178. eCollection 2019.PMID: 31730624. 2019

  7. Pollak, TA, Jonathan P. Rogers, Robert G. Nagele, Mark Peakman, James M. Stone, Anthony S. David, and Philip McGuire. Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders. Schizophrenia Bulletin doi:10.1093/schbul/sby021. 2018

  8. DeMarshall C, EL Goldwaser, A Sarkar, GA Godsey, NK Acharya, U Thayasivam, BA Belinkaf, and RG. Nagele. Autoantibodies as diagnostic biomarkers for the detection and subtyping of Multiple Sclerosis. Journal of Neuroimmunology 309:51-57. doi: 10.1016/j.jneuroim.2017.05.010. Epub 2017 May 19.PMID:28601288. 2017

  9. Acharya, NK, Xin Q, ELGoldwaser, GA Godsey, Hao Wu, MC Kosciuk, T Freeman, CH Macphee, RL Wilensky, V Venkataraman and RG Nagele. Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolemic pig model: Beneficial effects of the LpPLA2 inhibitor Darapladib. Diabetes and Vascular Disease Research, 2017 Mar 1:1479164116683149. doi: 10.1177/1479164116683149. 2017

  10. Goldwaser, Eric, Nimish K Acharya, Abhirup Sarkar, George Godsey, and Robert G Nagele. Breakdown of the cerebrovasculature and blood-brain barrier: a mechanistic link between diabetes mellitus and Alzheimer’s disease. Journal of Alzheimer’s Disease, 54:445-456. 2016

  11. DeMarshall CA, Nagele EP, Sarkar A, et al. Detection of Alzheimer’s disease at mild cognitive impairment and disease progression using autoantibodies as blood-based biomarkers. Alzheimer’s & Dementia : Diagnosis, Assessment & Disease Monitoring.3:51-62. doi:10.1016/j.dadm.2016.03.002. 2016

  12. DeMarshall CA, Han M, Nagele EP, Sarkar A, Acharya NK, Godsey G, Goldwaser EL, Kosciuk M, Thayasivam U, Belinka B, Nagele RG; Parkinson’s Study Group Investigators. Potential utility of autoantibodies as blood-based biomarkers for early detection and diagnosis of Parkinson's disease. Immunol Lett, 168(1): 80-8, 2015.

  13. DeMarshall C, Sarkar A, Nagele EP, Goldwaser E, Godsey G, Acharya NK, Nagele RG. Utility of autoantibodies as biomarkers for diagnosis and staging of neurodegenerative diseases. Int Rev Neurobiol, 122: 1-51, 2015.

  14. Acharya NK, Goldwaser EL, Forsberg MM, Godsey GA, Johnson CA, Sarkar A, DeMarshall C, Kosciuk MC, Dash JM, Hale CP, Leonard DM, Appelt DM, Nagele RG. Sevoflurane and Isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: Possible link to postoperative delirium and cognitive decline. Brain Res, 1620: 29-41, 2015.

  15. Acharya NK, Nagele EP, Han M, Nagele RG. Autoantibodies: double agents in human disease. Sci Transl Med, 5(186): 186fs19, 2013.

  16. Nagele EP, Han M, Acharya NK, DeMarshall C, Kosciuk MC and Nagele RG. Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease. PLoS ONE, 8(4): e660726, 2013.

  17. Acharya, NK, Levin EC, Clifford PM, Han M, Tourtellotte R, Chamberlain D, Pollaro M, Coretti NJ, Kosciuk MC, Nagele EP, Demarshall C, Freeman T, Guan C, Shi Y, Wilensky RL, Macphee CH, Nagele RG. Diabetes and hypercholesterolemia increase blood-brain barrier permeability and brain amyloid deposition: beneficial effects of the LpPLA2 inhibitor darapladib. J Alzheimers Dis, 35(1): 179-98. 2013.

  18. Acharya NK, Nagele EP, Han M, Coretti NJ, DeMarshall C, Kosciuk MC, Nagele RG. Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease. J Autoimmun, 38(4): 369-80. 2012.

  19. Han M, Nagele E, DeMarshall C, Acharya N, Nagele R. Diagnosis of Parkinson's disease based on disease-specific autoantibody profiles in human sera. PLoS One, 7(2): e32383, 2012.

  20. Nagele E, Han M, DeMarshall C, Belinka B, Nagele R. Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera. PLoS One, 6(8): e23112, 2011.

  21. Nagele RG, Clifford PM, Siu G, Levin EC, Acharya NK, Han M, Kosciuk MC, Venkataraman V, Zavareh S, Zarrabi S, Kinsler K, Patel N, Nagele EP, Dash J, Wang HY, Levitas A. Brain-reactive autoantibodies prevalent in human sera increase intraneuronal amyloid-β1-42 deposition. J Alzheimers Dis, 25: 605-622, 2011.

  22. Levin EC, Acharya NK, Han M, Zavareh SB, Sedeyn JC, Venkataraman V, Nagele RG. Brain-reactive autoantibodies are nearly ubiquitous in human sera and may be linked to pathology in the context of blood-brain barrier breakdown. Brain Res, 1345(23): 221-32, 2010.

Full Listing of Publications