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| First Name: | Thomas | | Last Name: | Wisniewski | | Title: | Professor of Neurology, Pathology and Psychiatry | | Advanced Degrees: | MD | | Affiliation: | New York University | | Department: | Neurology, Pathology and Psychiatry | | Street Address 1: | Millhauser lab, HN419 | | Street Address 2: | 550 1st Avenue | | City: | New York | | State/Province: | NY | | Zip/Postal Code: | 10016 | Country/Territory: | U.S.A. | | Phone: | 212-263-2152 | | Fax: | 212-263-7528 | | Email Address: |  |
Disclosure:
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Member reports no financial or other potential conflicts of interest. [Last Modified: 10 November 2008]
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View all comments by Thomas Wisniewski
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Polyglutamine Disorders (Huntington's, etc.), Stroke and Trauma, Tauopathies, Neuromuscular Disorders (ALS, etc.), Neurodevelopmental Disorders (Down syndrome, etc.), Alzheimer Disease, Parkinson Disease, Aging Process, Prion Diseases
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Brain imaging, Diagnosis, Protein structure/chemistry, Animal Models, Neuroimmunology, Drug screening, Molecular and Cell biology, A-beta PP/A-beta, Oxidative Stress, DNA microarrays, Proteomics, Tau/Cytoskeleton, Genetics, Microscopy, Neurobiology, Neuropathology, Chemistry/Pharmacology
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University, Medical hospital
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Dr. Wisniewski is a Professor of Neurology, Pathology and Psychiatry at NYU. He serves as the Director of the Conformational Disorders Laboratory, as well as being Director of the Memory and Dementia Disorders Center at NYU Medical Center. In addition, he is the Director of the Neuropathology Core of the NIH-funded NYU Alzheimer's Disease (AD) clinical center.
Dr. Wisniewski's laboratory focuses on gaining a better understanding of conformational disorders such as AD and prion related disease. This work has led to over 180 peer-reviewed publications. Key contributions have included discovering the role of apolipoprotein E in driving amyloid β accumulation in late-onset AD. Dr. Wisniewski's laboratory coined the term “pathological chaperone” to denote the role of apoE in disease, even prior to the discovery of linkage of apoE4 to late-onset AD. Using this hypothesis of the role of apoE in AD, Dr. Wisniewski has pioneered a potential novel approach to treat AD-related pathology by blocking the interaction of Aß and apoE. In addition, Dr. Wisniewski has been developing strategies for the prevention of amyloid β accumulation and its removal in AD using non-toxic, highly immunogenic Aβ homologous peptides as “vaccines”. This approach has been shown to be efficacious in a number of animal models of AD.
The use of this “vaccination” approach for prion disease was pioneered by Dr. Wisniewski's group. His laboratory has shown for the first time that both a passive and active vaccination approach is effective in animal and tissue culture models of prion disease. Significantly, Dr. Wisniewski's laboratory developed an oral mucosal prion vaccination, which is the first vaccine that has been shown to prevent prion peripheral infection in wild-type animals. In addition, Dr. Wisniewski’s laboratory was the first to show that metal chelation has potential as a novel therapeutic approach for prion diseases.
Dr. Wisniewski's laboratory has also been active in the development of diagnostic methods for the detection of amyloid deposits in both AD and prion disease byMRI and 2-photon microscopy.
These various studies by Dr. Wisniewsk's laboratory have helped direct our greater understanding of abnormal protein accumulation in the brain towards diagnostic and therapeutic interventions.
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1. Wisniewski T, Frangione B. Apolipoprotein E: a pathological chaperone in systemic and cerebral amyloidoses. Neuroscience Letters 1992; 135:235-238.
2. Sigurdsson EM, Scholtzova H, Mehta PD, Frangione B, Wisniewski T. Immunization with a non-toxic/non-fibrillar amyloid-ß homologous peptide reduces Alzheimer’s disease associated pathology in transgenic mice. American Journal of Pathology, 159: 439-447, 2001.
3. Sigurdsson E, Brown DR, Daniels M, Kascsak RJ, Kascsak R, Carp R, Meeker HC, Frangione B, Wisniewski T. Vaccination delays the onset of prion disease in mice. American Journal of Pathology, 161: 13-17, 2002.
4. Zaim Wadghiri Y, Sigurdsson EM, Sadowski M, Elliot JI, Li Y, Scholtzova H, Tang CY, Aguilnaldo G, Pappolla M, Duff K, Wisniewski T*, Turnbull DH* (*joint senior authors). Detection of Alzheimer’s amyloid in transgenic mice using magnetic resonance micro-imaging. Magnetic Resonance in Medicine, 50: 293-302, 2003.
5. Sadowski M, Pankiewicz J, Scholtzova H, Tsai J, Li Y, Carp RI, Meeker HC, Gambetti P, Debnath M, Mathis CA, Li S, Gan WB, Klunk WE, Wisniewski T. Targeting prion amyloid deposits in vivo using methoxy-X04, Journal of Neuropathology and Experimental Neurology, 63: 775-784, 2004.
6. Goni F, Knudsen E, Schreiber F, Scholtzova H, Pankiewicz J, Carp R, Meeker HC, Brown DR, Chabalgoity JA, Sigurdsson EM, Wisniewski T. Mucosal vaccination delays or prevents prion infection via an oral route. Neuroscience, 133: 413-421, 2005.
7. Sadowski MJ, Pankiewicz J, Scholtzova H, Mehta PD, Prelli F, Wen P, Quartermain D, Wisniewski T. Blocking the Apolipoprotein E/Amyloid-ß Interaction as a Potential Therapeutic Approach for Alzheimer's Disease. Proceedings of the National Academy of Science, 49: 18787-18792, 2006.
8.Sigurdsson EM, Wadghiri YZ, Mosconi L, Blind JA, Knudsen E, Asuni A, Tsui WH, Sadowski M, Turnbull DH, de Leon M, Wisniewski T. A non-toxic ligand for voxel-based MRI analysis of plaques in AD transgenic mice. Neurobiology of Aging, 29: 836-847, 2008.
9. Goni F, Chabalgoity JA, Prelli F, Schreiber F, Scholtzova H, Chung E, Kascsak R, Kascsak R, Brown DR, Sigurdsson EM, Wisniewski T. High titers of mucosal and systemic anti-PrP antibodies abrogates oral prion infection in mucosal vaccinated mice. Neuroscience, 153: 679-686, 2008.
10. Wisniewski T, Konietzko U. Amyloid-β immunisation for Alzheimer's disease. Lancet Neurology, 7(9):805-811, 2008.
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What is the cause of late-onset sporadic AD? |
1. Bertram L, Tanzi RE. Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci. 2008 Oct;9(10):768-78.
2. Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci. 2008 Aug 13;28(33):8354-60.
3. Yuzwa SA, Macauley MS, Heinonen JE, Shan X, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ, Vocadlo DJ. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol. 2008 Aug;4(8):483-90
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Late-onset AD is related to poor clearance of Aß peptides/oligomers, with ApoE as one important factor. Blocking the interaction between Aß and apoE is an effective therapeutic intervention.
Vaccination and beta-sheet binding ligands will work for the treatment and diagnosis of both AD and prion diseases. |
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