Advances in Research

Date Milestone Details
May 1997

Drs Ekaterina Rogaeva, Peter St George-Hyslop, and others provide evidence confirming the existence of a gene on chromosome 12 (the identity of which is still unknown) which causes susceptibility to late-onset Alzheimer’s disease. This work shows that, in addition to a gene on chromosome 12, there must be at least one other gene causing susceptibility to this disease which has yet to be mapped.

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.

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 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.

September 1995

Drs Howard Mount, Cheryl Dreyfus and Ira Black discover glial cell-line-derived neurotrophic factor (GDNF) to be the most potent survival and development-promoting factor for Purkinje cells. Purkinje cells are output neurons of the cerebellum and are targeted for degeneration in a broad range of disorders, including hypothyroidism, autism, hereditary ataxias, certain forms of cancer and drug toxicity. This discovery led to trials of GDNF in animal models of Purkinje cell degeneration.

August 1995

Dr. Peter St George-Hyslop and his team of international scientists discover a second gene (Presenilin 2 - located on chromosome 1) responsible for a less severe form of familial early-onset Alzheimer’s disease.

June 1995

Dr. Peter St George-Hyslop and international colleagues announce that they have identified and cloned the defective gene (Presenilin 1) that causes the most virulent form of Alzheimer’s Disease (located on chromosome 14).

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.

September 1994

A mutation in CuZnSOD, an enzyme linked to familial ALS, is discovered. Analysis of the biochemistry and function of this enzyme in the brain at the CRND by Drs William Tatton, Peter St George-Hyslop and Don Crapper McLachlan clarifies the cause and propagation of ALS.

May 1994

Drs Peter St George-Hyslop, Don Crapper McLachlan and others show that different genes causing susceptibility to Alzheimer’s disease interact. This interaction provides strong evidence for the existence of a multi-step metabolic pathway governing the initial stages of susceptibility to Alzheimer’s disease.

September 1993

The Apolipoprotein e 4 variant is found to be a risk factor for Alzheimer’s disease by a collaborative team led by Dr. A.D. Roses of Duke University that included Dr. Peter St George-Hyslop at the Tanz Centre.

December 1992

Drs Peter St George-Hyslop, Don Crapper McLachlan and others report that chromosome 14 contains a gene (at that time unidentified) which causes the early onset of familial Alzheimer’s Disease.

May 1992

Drs Harry Karlinsky, Peter St George-Hyslop and Don Crapper McLachlan describe the first Canadian case of familial Alzheimer’s Disease due to a mutation in the amyloid precursor protein gene. 

September 1990

Drs Peter St George-Hyslop, Don Crapper McLachlan and others show that Alzheimer’s Disease is a complex disorder with multiple etiologies, some of which are genetic.  This discovery causes a significant shift in experimental paradigms used by all Alzheimer’s Disease researchers because it had previously been assumed that Alzheimer’s Disease was a single 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.

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