Thomas Wisniewski, M.D., is currently Associate Professor of Neurology, Pathology and Psychiatry at New York University School of Medicine. After graduating from King's College School of Medicine (London), he did a Neurology Residency at New York University and a Neuropathology Residency at Columbia-Presbyterian Hospital, where he was Chief Resident of Neurology and Pathology, respectively. Dr. Wisniewski is Board Certified in both Neurology and Neuropathology. Following his residencies, Dr. Wisniewski did post doctoral training in the laboratory of Prof. Blas Frangione at NYU. Soon after Dr. Wisniewski became the PI of the Neurodegenerative Conformational Disorders Laboratory at NYU, which focused on understanding the mechanisms which drive amyloid deposition in Alzheimer's disease and in other neurodegenerative conditions. Work at the laboratory has lead to over 100 peer-reviewed publications. The aim of his work has been to direct this greater understanding toward therapeutic interventions. Key discoveries have included discovering the role of apolipoprotein E in driving amyloid deposition in late-onset AD. Dr. Wisniewski coined the term "pathological chaperone" to denote the role of apoE, prior to the discovery of the linkage of apoE4 to late-onset AD. Dr. Wisniewski's laboratory has also biochemically characterized the interactions between apoE and amyloid β. More recently, Dr. Wisniewski has been developing strategies for the removal of amyloid both in AD using non-toxic, highly immunogenic proteins as "vaccines". This approach has been shown to be efficacious in both animal models of AD and prion disease. This approach is likely to be superior to the methodologies used by Schenk and the Elan group in their recent ill fated clinical trial. Dr. Wisniewski and his group predicted that amyloid β toxicity will be a problem in this trial and his vaccine approach is aimed at avoiding these potential safety concerns. He has also been working at using the novel "vaccination" approach for a broader list of neurodegenerative diseases, which are called "conformational disease". His recent work has shown that this approach works in the animal models of prion disease.

Importance of published article

Dr. Wisniewski's work has helped to clarify the interactions between apolipoprotein E and amyloid β (Aβ), showing that apoE can directly promote Aβ fibril formation. In addition, Dr. Wisniewski has worked in collaboration with Dr. Jorge Ghiso showing that Aβ peptides can cross the blood-brain barrier (BBB) from the systemic circulation into the brain. In his JAD paper: "Amyloid β40/42 clearance across the blood-brain barrier following intra-ventricular injections in wild-type, apoE knock-out and human apoE3 or E4 expressing transgenic mice", Dr. Wisniewski also demonstrated that Aβ peptides, in particular Aβ1-40, can cross the BBB into the systemic circulation rapidly. This is the first study of Aβ peptide passage across the BBB from the brain. The observation that Aβ1-40 is rapidly cleared, has significance for the present passive and active immunization approaches to reduce amyloid burden. Since Aβ can rapidly exit from the brain into the systemic circulation, as shown in this paper, increasing peripheral clearance of Aβ should be sufficient to reduce the amyloid burden within the brain, without the need for antibodies (or other Aβ binding agents) to cross the BBB (where they are more likely to be associated with inflammatory, toxic side-effects). The paper also demonstrates that this BBB passage of Aβ peptides does not appear to be influenced by apoE isotype expression