Neurodegenerative Conformational Disorders Laboratory
Director: Thomas Wisniewski, M.D.

Work at the Neurodegenerative Conformational Disorders Laboratory has focused on understanding the mechanisms which drive amyloid deposition in Alzheimer's disease and in other neurodegenerative conditions. Studies at the laboratory have lead to over 100 peer-reviewed publications and a number of awards from funding agencies such as the National Institute on Aging and the Alzheimer's Disease Association. The thrust of the laboratory has been to translate the growing understanding of the basic pathogenesis of Alzheimer's disease and other similar disorders towards effective 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 apolipoprotein E, even prior to the discovery of the linkage of apolipoprotein E to late onset AD. The laboratory has produced numerous publications showing that apoE can directly interact with amyloid b peptides to promote amyloid formation under certain circumstances and that apoE has a role in amyloid b peptide clearance. The laboratory has also worked on defining the role of other proteins which are linked genetically to AD, such as presenilin 1, showing that presenilin 1 regulates disassembly of adherens junctions and influences neurite outgrowth. In addition, the laboratory has worked on other forms of cerebral amyloidosis, leading to the characterization of a novel form of amyloid deposition, related to transythretin, called Hungarian Amyloidosis.

More recently, Dr. Wisniewski, in collaboration with other researchers, 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.The methodology of this vaccine may be superior to the approach used by Schenk and the Elan group in their recent ill fated clinical trial. Dr. Wisniewski and his group predicted that Ab toxicity would 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 this "vaccination" approach for a broader list of neurodegenerative diseases, which are called "conformational disease".

Dr. Wisniewski’s recent work has shown that this approach works in the animal models of prion disease. Prion diseases currently have no effective therapy and are a rapidly fatal form of neurodegeneration. Other ongoing projects include the development of methods for the detection of amyloid deposits by magnetic resonance imaging. These recent experiments hold the promise that more definitive early diagnosis and more effective therapeutic interventions will be possible for both Alzheimer's disease and prion diseases in the future.