Advances in Research

Date Milestone Details
June 2000

Merck Sharp Dohme & Bristol-Myers Squibb announce that they have developed compounds that bind to the presenilin proteins (first isolated at the CRND in 1995) and that inhibit the production of the neurotoxic amyloid β-peptide. Bristol-Myers Squibb compound enters Phase I trials as a novel therapeutic for Alzheimer’s disease in the US.

April 2000

Drs JoAnne McLaurin and Paul Fraser discover inositol stereoisomers that inhibit amyloid formation and form complexes that are non-toxic to neurons, the primary targets of destruction in Alzheimer’s disease. This discovery will enable the development of an anti-amyloid drug therapy for Alzheimer’s disease.


Tanz Centre scientists identify several extended families with mutations in the Parkin, DJ-1, PINK1, LRRK2 and GBA genes.

January 2000

In collaboration with Lindsay Farrer of Boston University, and others, Drs Peter St George-Hyslop and Ekaterina Rogaeva show that variants in the angiotensin-converting enzyme (ACE) are associated with susceptibility to sporadic Alzheimer’s disease in certain age groups.

2000 - 2006

Tanz Centre scientists identify several extended families with mutations in the Parkin, DJ-1, PINK1, LRRK2 and GBA genes.

December 1999

In collaboration with Dr. T. Katayama from Osaka University in Japan, Dr. Peter St George-Hyslop and others show that the presenilin 1 gene is involved in the metabolism of several important proteins, including the β-amyloid precursor protein and a protein involved in the unfolded protein response in the endoplasmic reticulum of cells.

December 1999

Drs D. Grimes, Catherine Bergeron, and Anthony Lang demonstrate that dementia is the most common presentation of corticobasal degeneration.

November 1999

Using a number of biophysical approaches, Drs Paul Fraser, Christopher Yip and Avi Chakrabartty identify a potentially key element that may mediate the assembly of intracellular amyloid, which is thought to play a central role in neurodegeneration.

October 1999

Dr. David Westaway clones the Doppel gene, which provides new insights into the biology of the PrP protein involved in human Creutzfeldt-Jakob Disease and into scrapie and bovine spongiform encephalopathy (Mad Cow Disease) in animals.

September 1999

Using a novel imaging method called atomic force microscopy, Drs Paul Fraser, JoAnne McLaurin and Christopher Yip discover a sequence of events that mediates the neurotoxicity of amyloid in Alzheimer’s disease.

July 1999

Drs Peter St George-Hyslop, David Westaway and Paul Fraser develop a robust animal model system which replicates most of the clinical features of human Alzheimer’s disease. This will expedite the discovery and testing of new diagnostics and treatments for Alzheimer’s disease.

January 1999

Drs Masaki Nishimura, Gang Yu, David Westaway, Howard Mount, Paul Fraser, Peter St George-Hyslop and others show that mutations in the presenilin proteins which cause Alzheimer’s disease affect the function of a high molecular weight protein complex. This provides impetus for work to identify the other components of the complex, and eventually leads to the identification of nicastrin (see July 2000). The latter molecule, when mutated, also alters the metabolism of the β-amyloid precursor protein.

August 1998

Based upon research into therapeutics by Drs Paul Fraser, Robert Kisilevsky and Francine Gervais, a new drug for the treatment for amyloid plaques enters Phase II trials and is granted FDA approval (April 1999). Related compounds enter Phase 1 for the treatment of Alzheimer’s disease in collaboration with Lundbeck Pharmaceuticals (Copenhagen).

July 1998

Drs Catherine Bergeron and Neil Cashman assume the leadership of the Neuropathology and Clinical surveillance arms of the Canadian Creutzfeldt-Jakob Disease (CJD) Surveillance Program sponsored by Health Canada, which monitors CJD in Canada.

July 1998

Dr. JoAnne McLaurin discovers that during the natural aging progression, the normally tight regulation of immune functions within the central nervous system is compromised. This dysregulation was shown to contribute to the enhanced sensitivity of the aging brain to insults such as amyloid.

June 1998

Drs Howard Mount, Cheryl Dreyfus and Ira Black describe a molecular survival/death switch responsible for regulating the Purkinje cell fate upon exposure to nerve growth factor. This discovery challenges the orthodox notion that nerve growth factor has only positive effects on developing neurons. He and his group later go on to demonstrate the specific failure of this switch in a genetic mouse model of ataxia telangiectasia, a pediatric degenerative disease associated with massive Purkinje cell death.

July 1997

Dr. Catherine Bergeron establishes the first and only dedicated laboratory for the diagnosis of, and research on, human prion diseases.

July 1997-99

Drs Howard Mount, Kuo Wu, Eric Levine and Ira Black publish four papers that report an unsuspected function of brain-derived neurotrophic factor (BDNF) in controlling status of N-methyl-D-aspartate receptors. Together, these results suggest a potential mechanism for growth-factor-induced potentiation of synaptic transmission, the putative molecular correlate of learning.

July 1997

Dr. Peter St George-Hyslop, in collaboration with Drs. Steven Post, Peter Whitehouse at Case Western Reserve University in Cleveland, and others, provide a framework for the ethical application of clinical genetic testing for Alzheimer’s disease.

June 1997

Dr. Catherine Bergeron recognizes that involvement of the neocortex is a frequent event in progressive supranuclear palsy.