Advances in Research

Datesort descending Milestone Details
December 2000

Drs Peter St George-Hyslop, David Westaway and Chris Janus generate a powerful transgenic mouse model of Alzheimer’s disease and show that vaccination of this mouse with Aβ has dramatic effects on memory and brain pathology. This work shows that Aβ vaccination (and other therapies which block or inhibit Aβ) might be used to treat Alzheimer's disease.

December 2000, November 2002

Tanz Centre researchers make two important findings: the discovery that antibodies to Aβ can block cognitive decline in mouse models of AD, and the discovery of the precise part of Aβ that these antibodies must bind to in order to block AD. These two discoveries encourage the use of immune (active or passive vaccine-based) therapies for AD in humans, and the refinement of these immune therapies to avoid induction of allergic encephalitis (an occasional complication of vaccination with the full-length Aβ-peptide).

December 2001, December 2004

Tanz Centre researchers define the antagonistic activities of PrP and Doppel in Tg mice.

December 2004

Tanz Centre scientists invent a cellular assay for the prion protein protective effect.

December 2006

The Tanz Centre becomes the first to identify FTD-causing mutations in the IFT74 gene on chromosome 9.

February 1997

Drs Paul Fraser, Margaret Sunde, Colin Blake and Mark Pepys determine the molecular process of amyloid formation in a lysozyme model. The findings have wide-ranging implications for our understanding of amyloid deposition and the development of new treatment strategies.

February 2007

Tanz Centre scientists report that inherited variants in the neuronal sorting receptor, SORL1, are associated with late-onset Alzheimer’s disease in different ethnic groups. This study emphasizes the complexity of the genetics of the common late-onset form of Alzheimer’s disease. The study included multiple Centers and tested ~7,000 DNA samples from Caucasians, Hispanics, Arab Israelis and African Americans and uncovered two consistent patterns that linked the SORL1 gene to AD. These AD-associated variants may down-regulate tissue-specific expression of SORL1. They also show that SORL1 directs trafficking of APP into recycling pathways, and that when SORL1 is under-expressed, APP is sorted into Aβ-generating compartments. Hence, the inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing common late-onset form of Alzheimer’s disease.

January 1990

The Tanz Centre for Research in Neurodegenerative Diseases (CRND) was established in 1990 as a partnership between the University of Toronto, the Alzheimer Society of Ontario and several generous private donors, most notably Dr. Mark M. Tanz.

January 1995

Using mouse models and in vitro systems, Drs Paul Fraser, Robert Kisilevsky and Walter Szarek develop a new series of anti-amyloid compounds that control the deposition of systemic amyloid plaques. This discovery launches investigations into the development of novel approaches for the treatment of Alzheimer’s disease and related disorders, and the establishment of the biotechnology company, Neurochem Inc.

January 1996

Drs Howard Mount and Kuo Wu determine that the neurotransmitter, nitric oxide, regulates its own synthesis by activating synaptic calmodulin kinase, an enzyme that in turn inhibits nitric oxide synthase. Nitric oxide is a putative initiator of brain cell death associated with oxidative stress. Knowledge of how neuronal oxide synthase is normally turned off has provided a candidate mechanism for pharmacologically intervening in brain cell death.

January 1996

Dr. Catherine Bergeron demonstrates that neurofilament expression is down-regulated in substantia nigra neurons in Parkinson’s disease. Neurofilament down-regulation also takes place in Alzheimer disease’s and ALS and is assumed to represent a non-specific response to neurodegeneration.

January 1996

Dr. Catherine Bergeron maps the expression of the antioxidant enzyme SOD-1 in the human brain. The enzyme is abundant throughout the brain and does not correlate with areas susceptible to neurodegeneration; it is much less abundant in regions most sensitive to hypoxic damage.

January 1997

Drs Peter St George-Hyslop and David Westaway, in collaboration with Martin Citron and Dennis Selkoe at Harvard University, show that mutations in the presenilin proteins cause Alzheimer’s disease by altering the metabolism of the β-amyloid precursor protein, with a consequent overproduction of the amyloid β-protein. Taken in conjunction with prior evidence of the biochemical effects of the other Alzheimer’s disease genes, this report provides compelling evidence that Alzheimer’s disease is initiated by abnormalities in the metabolism of the β-amyloid precursor protein and the overproduction/reduced clearance of the amyloid β-peptide.

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.

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.

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.

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 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.

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.