Advances in Research

Date Milestone Details

Tanz CRND scientists revealed that the C9orf72 G4C2 repeat itself is the main site of DNA methylation. By developing a novel assay, they demonstrated that the G4C2-repeat expansion is methylated in carriers of >90 repeats (100%), while the intermediate (22-90 repeats) and small (<22 repeats) alleles are unmethylated. The presence of G4C2-methylation was identified in both blood and brain tissues, implying its use as a biomarker. This study contributed to understanding the consequences of expansion and might help to establish a more accurate cut-off for pathogenic repeat. For instance, our investigation of a large ALS family revealed that a 70-repeat allele from the unaffected father expanded during parent-offspring transmission and started the first generation affected by ALS (four children carry ~1,750-repeats). Epigenetic and RNA-expression analyses further discriminated the large expansions (methylated and associated with reduced C9orf72 expression) from the 70-repeat allele (unmethylated and associated with up-regulation of C9orf72). The small expansions might be considered ‘‘pre-mutations’’ to reflect their propensity to expand in the next generation. These findings support a hypothesis of multiple origins for the expansion; and might help explain the high frequency of sporadic ALS/FTD patients (e.g., 21% among Finnish ALS subjects).


Tanz Centre scientists conducted the first epigenetic study of C9orf72 underlying silencing of C9orf72 expression. It was revealed that DNA hypermethylation of the CpG island 5’ of the repeat is associated with the presence of expansion; and a higher degree of methylation was correlated with shorter disease duration and with familial ALS.

2013 and 2015

The genome-wide study by Tanz CRND scientists revealed that Alzheimer’s disease is linked to recessive inheritance that can be related to the presence of long runs of homozygosity (ROHs). First, we investigated an inbred population of Caribbean Hispanics and obtained evidence that ROHs could be a significant contributor to the etiology of Alzheimer’s disease. For instance, people with Alzheimer’s disease have longer ROHs than controls; a clue that recessive genes are lurking in those parts of the genome [Ghani, et al, JAMA Neurol 2013]. Second, we led the international genetic consortium to conduct ROH-analysis of the largest African American dataset [Ghani, et al, JAMA Neurol, 2015]. This is an essential study, since the risk of Alzheimer’s disease among African Americans is up to three times higher than among Caucasians. The value of our study is in the identification of cases with a higher probability of having rare mutations, which could make the search for mutations cost-efficient.

June 2012

Tanz Centre researcher participates in a committee to harmonize the neuropsychological assessment of patients presenting with cognitive complaints to the five academic memory clinics associated with the University of Toronto. The aim is to create a short battery that could be used by physicians and residents to assess all cognitive domains without having to wait for a full neuropsychological assessment. The tool will enable a uniform data acquisition. The standardisation of the battery will facilitate research amongst the cognitive behavioral groups at UofT. This tool will also help residents rotating in our clinics learn how to test the different cognitive domains and this information will be used to help make a diagnosis and assess functional impact.

June 2012

Tanz Centre researchers lead a large international study estimating the contribution of C9ORF72 repeat expansion in four neurodegenerative diseases. They demonstrate that the hexanucleotide expansion in C9orf72 gene is a common cause of Amyotrophic lateral sclerosis and Frontotemporal Dementia, but not of Alzheimer’s disease or Parkinson’s disease.

April 2012

Tanz Centre scientists demonstrate early and progressive loss of noradrenaline in the TgCRND8 mice. They demonstrate that these deficits coincided with the onset of cortically encoded memory impairment and BDNF dysregulation. They also demonstrate that the neurochemical deficits and the AD-like behaviours could be reversed with a presynaptic alpha-2-adrenergic receptor antagonist that increases noradrenergic and cholinergic transmission.


Tanz Centre scientists show that immuno-targeting of monomer/misfolded SOD1 may have therapeutic potential for the treatment of Amyotrophic Lateral Sclerosis caused by mutations in SOD1.


Tanz Centre researchers provide the first glimpse into a molecular biology that ties the prion protein to its ZIP transporter molecular cousins and suggests that cellular zinc starvation plays a role in prion disease - evidence that a subset ZIP metal ion transporters which contain a prion protein-like ectodomain can interact with the cellular prion protein and undergo abnormal cleavages in prion disease.

October 2011

Tanz Centre scientists contribute to the discovery of novel hexanucleotide (GGGGCC) repeat expansion in the C9orf72 gene, which is responsible for two common neurodegenerative disorders: amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation explains 46% familial and 21% sporadic ALS in the Finnish population; and also presents in ~30% familial ALS and ~20% familial FTD cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases.

Tanz Centre scientists identify RNA targets of the TAR-DNA Binding Protein (TDP-43) and show that some of these are deregulated in Amyotrophic Lateral Sclerosis.

Tanz Centre scientists discover that heterogeneity of neuropatholgical changes in athletes with multiple concussions- not all is chronic traumatic encephalopathy.

Tanz Centre scientists participate in a consortium identifying Common variants that affect risk for the tauopathy in Progressive Supranuclear Palsy.

October 2011

Tanz CRND celebrates its 20th anniversary.

July 2011

Tanz Centre researcher creates a clinical intake tool that will be used by the five academic memory clinics associated with the University of Toronto. This tool will enable a uniform data acquisition when conducting an interview with a patient with cognitive complaints, in addition to a standard neurological exam. The standardisation of approach to the patient with cognitive complaints will facilitate research amongst the cognitive behavioral groups at UofT. This tool will also help residents rotating in our clinics learn about the different cognitive domains and how to probe for changes in personality, cognition and social cognition. This tool will initially be rolled out to the UofT memory clinics with the view of having it used across Ontario, and perhaps across Canada, so that a nationwide registry of patients with cognitive impairment could be established and queried for epidemiological research on health care necessities and outcomes.

May 2011

Tanz Centre scientists contribute to the discovery of several novel genes associated with late-onset Alzheimer's disease: MS4A4/MS4A6E, CD2AP, CD33 and EPHA1.

May 2010

Tanz Centre scientists uncover deficits in entorhinal cortical function in TgCRND8 mice and linked these to alterations in cortical BDNF expression.


Tanz Centre scientists develop a new antibody recognizing unfolded SOD1, USOD antibody, and show that inclusions containing TAR DNA Binding Protein (TDP-43) or misfolded SOD1 are non-amyloidogeneic.

November 2009

the Centre for Drug Research and Development and MaRS Innovation announces a new collaboration on projects of mutual interest with a goal to advance and commercialize early-stage health-related discoveries. The first project funded under the arrangement saw Prof. Paul Fraser working with the University of British Columbia's Dr. Bruce Verchere, to investigate amyloid aggregation inhibitors as a novel approach to address the treatment of diabetes.

October 2009

Tanz Centre researchers lead a large collaborative study demonstrating that GBA gene (known to be responsible for Gaucher’s Disease) is among the most significant Parkinson’s disease risk factors indentified to date. They reveal that clinically, subjects with a GBA mutation presented earlier, and were more likely to have affected relatives and atypical manifestations.

July 2009

Tanz Centre scientists demonstrate a common reduction in BDNF expression across multiple lines of APP-transgenic mice.

March 2009

For the first, Tanz Centre researchers address the mechanism responcible for low penetrance of a novel SOD1 deletion in the ALS family. They demonstrate that the enhanced splicing of SOD1 exon 2 acts as a natural knock-down of the mutant SOD1 allele leading to a mild disease presentation (Rogaeva)


The Centre for Research in Neurodegenerative Diseases is officially renamed The Tanz Centre for Research in Neurodegenerative Diseases

Tanz Centre scientists show, using a novel antibody, SEDI antibody, that superoxide dismutase-1 (SOD1 ) is misfolded in cases of Amyotrophic Lateral Sclerosis caused by mutations in SOD1.

2009 - 2011

Tanz Centre researchers discover the evolutionary descent of  prion proteins from a larger family of ZIP metal ion transporters.The prion protein is responsible for a group of fatal neurodegenerative diseases that include Creutzfeldt-Jakob disease (CJD) in humans and Bovine Spongiform Encephalopathy (BSE) in cattle. Work at the institute establishes the evolutionary origin of the prion gene family to be the result of a genomic insertion of a spliced and C-terminally truncated transcript of a ZIP metal ion transporter, thus leading to the proposition that the prion founder gene constituted a retrogene. These data explain the hitherto puzzling characteristics of the prion protein as remnants of an ancient function in the sensing and transport of metal ions.