William Van Nostrand
Co-Director, Ryan Institute
Herrmann Professor of Neuroscience
Professor of Biomedical and Pharmaceutical Sciences
Bill Van Nostrand has been working in Alzheimer’s disease and related disorders (ADRD) research for more than 30 years. He is one of the field’s leading researchers on the pathogenesis of cerebral amyloid angiopathy, cerebral small vessel disease, and Alzheimer’s disease using biochemical, molecular, cellular and animal model approaches. He is noted for developing transgenic animal models of disease that have provided key insights into disease processes. His current collaborations include work at Yale University; Stony Brook University; universities in the Netherlands including Radboud University Medical Center in Nijmegen, Leiden University Medical Center in Leiden, and Amsterdam University Medical Center in Amsterdam; and Alnylam Pharmaceuticals in Cambridge, Massachusetts.
Originally trained as a biochemist, Dr. Van Nostrand is recognized as the first to purify and characterize amyloid precursor protein (APP), the progenitor of amyloid-beta (A-beta), a key component involved in the pathogenesis of ADRD. He has more than 150 publications in journals including Nature, Science, Nature Communications, The Lancet, Neuron, and Proceedings of the National Academy of Sciences. Dr. Van Nostrand holds several patents, and has served on numerous national and private advisory committees for the National Institutes of Health. He is a recipient of a Research Career Development Award from the NIH and the Alzheimer’s Association Zenith Award in recognition of his contributions to the field of Alzheimer’s disease research.
Dr. Van Nostrand received his Ph.D. in biological sciences from University of California, Irvine, where he was also a postdoctoral fellow in biochemistry prior to joining the faculty as a Research Assistant Professor and Associate Adjunct Professor. He is Professor Emeritus in the Department of Neurosurgery at Stony Brook University, where he spent 20 years on the faculty prior to joining the George & Anne Ryan Institute for Neuroscience in 2017, along with colleague John Robinson.
Since arriving at URI, he has attracted more than $10 million dollars in NIH and private support and is an active mentor to Ryan Institute junior faculty in grant applications and career development.
The Van Nostrand Lab
Impact of non-pharmacological chronic hypertension on a transgenic rat model of cerebral amyloid angiopathy. Stanisavljevic A*, Schrader JM*, Zhu X*, Mattar JM*, Hanks A*, Xu F*, Majchrzak M*, Robinson JK*, Van Nostrand WE*. Frontiers in Neuroscience, March 2022.
Elevated expression of urokinase plasminogen activator in rodent models and patients with cerebral amyloid angiopathy. Vervuurt M, Zhu X, Schrader J, de Kort A, Marques TM, Kersten I, Kuiperji HB, Klijn CJM, Van Nostrand WE*, and Verbeek MM. Neuropathology and Applied Neurobiology, March 2022.
rTg-D: A novel transgenic rat model of cerebral amyloid angiopathy type-2. Davis J, Xu F, Zhu X, and Van Nostrand WE. Cerebral Circulation – Cognition and Behavior, March 2022.
Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries. Chen X, Liu X, Koundal S, Elkin R, Zhu X, Monte B, Xu F, Dai F, Pedram M, Lee H, Kipnis J, Tannenbaum A, Van Nostrand WE, Benveniste H. Nature Aging, February 2022.
Normal cerebrospinal fluid concentrations of PDGFRβ in patients with cerebral amyloid angiopathy and Alzheimer’s disease. De Kort AM, Kuiperij HB, Kersten I, Versleijen AAM, Schreuder FHBM, Van Nostrand WE*, Greenberg SM, Klijn CJM, Claassen JAHR, Verbeek MM. Alzheimer’s & Dementia, December 2021.
Emergent white matter degeneration in the rTg-DI rat model of cerebral amyloid angiopathy exhibits unique proteomic changes. Schrader JM*, Xu F*, Lee H, Barlock B, Benveniste H, Van Nostrand WE*. American Journal of Pathology, December 2021.
Human cerebral vascular amyloid contains both antiparallel and parallel in-register Aβ40 fibrils. Irizarry BA, Davis J*, Zhu X*, Boon BDC, Rozemuller AJM, Van Nostrand WE*, Smith SO. Journal of Biological Chemistry, November 2021.
Distinct brain regional proteome changes in the rTg-DI rat model of cerebral amyloid angiopathy. Schrader JM*, Xu F*, Van Nostrand WE*. Journal of Neurochemistry, October 2021.
Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy. Lee H, Xu F*, Liu X, Koundal S, Zhu X*, Davis J*, Yanez D, Schrader J*, Stanisavljevic A*, Rothman DL, Wardlaw J, Van Nostrand WE*, Benveniste H. Journal of Cerebral Blood Flow and Metabolism, May 2021.
Anti-Parallel β-Hairpin Structure in Soluble Aβ Oligomers of Aβ40-Dutch and Aβ40-Iowa. Ziao F, Van Nostrand WE*, Smith SO. International Journal of Molecular Science, January 2021.
Additional Selected Publications
A novel transgenic rat model of robust cerebral miscrovascular amyloid with prominent vasculopathy. Davis, J., Xu, F., Hatfield, J., Lee H., Hoos, M.D., Popescu, D., Crooks, E., Kim, R., Smith, S.O., Robinson, J.K., Benveniste, H., and Van Nostrand, W.E. American Journal of Pathology 188:2877-2889 (2018)
Intensive “brain training” intervention fails to reduce amyloid pathologies or cognitive deficits in transgenic mouse models of Alzheimer’s disease. Anderson, M., Xu, F., Ou-Yang, M.H., Davis, J., Van Nostrand, W.E. and Robinson, J.K. Journal of Alzheimer’s Disease 55:1109-1121 (2017)
Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid b-protein precursor abolishes its anti-thrombotic properties in vivo. Xu, F., Davis, J. and Van Nostrand, W.E. Thrombosis Research (2017)
Cerebral vascular amyloid seeds drive amyloid b-protein fibril assembly with a distinct anti-parallel structure. Xu, F., Fu, Z., Dass, S., Kotarba, A.E., Davis, J., Smith, S.O. and Van Nostrand, W.E. Nature Communications 7:13527 (2016)
The N-terminal region of myelin basic protein reduces fibrillar amyloid b-protein deposition in Tg-5xFAD mice. Ou-Yang, M., Xu, F., Liao, M.-C., Davis, J., Robinson, J.K., and Van Nostrand, W.E. Neurobiology of Aging 36:801-811 (2015)
Mechanism of nucleated conformational conversion of Ab42. Fu, Z., Aucoin, D.S., Davis, J., Van Nostrand, W.E., and Smith, S.O. Biochemistry 54:4197-4207 (2015)
Cerebral microvascular rather than parenchymal amyloid b-protein pathology promotes early cognitive impairment in transgenic mice. Xu, W., Xu, F., Anderson, M.E., Kotarba, A.E., Davis, J., Robinson, J.K., and Van Nostrand, W.E Journal of Alzheimer’s Disease 38:621-632 (2014)
Early-onset formation of parenchymal plaque amyloid abrogates cerebral microvascular amyloid accumulation in transgenic mice. Xu, F., Kotarba, A.E., Ou-Yang, M.H., Fu, Z., Davis, J., Smith, S.O., and Van Nostrand, W.E. Journal of Biological Chemistry 289:17895-17908 (2014)
Capping of Ab42 oligomers by small molecule inhibitors. Fu, Z., Aucoin, D., Ahmed, M., Ziliox, M., Van Nostrand, W.E., and Smith, S.O. Biochemistry 53: 7893-7903 (2014)
Fine mapping of the amyloid b-protein binding site on myelin basic protein. Kotarba, A., Aucoin, D., Hoos, M.D., Smith, S.O., and Van Nostrand, W.E. Biochemistry 52:2565-2573 (2013)