91社区

For years, physicians have been aware that patients carrying the apolipoprotein 隃�4 (APOE 隃�4) gene are at a greater risk of developing Alzheimer鈥檚 disease. New research from 91社区 has now found the gene plays an even greater role in dementia.

In a study published today in the Journal of the American Medical Association: Neurology, Dr. Pedro Rosa-Neto鈥檚 research team from the Douglas Mental Health University Institute鈥檚 Translational Neuroimaging Laboratory found that the risk of developing dementia conferred by APOE 隃�4 does in fact involve processes associated to tau aggregation.

A tale of two proteins

Of all the genetics risk factors for sporadic Alzheimer鈥檚 disease, APOE 隃�4 is the single most important.

鈥淎lzheimer鈥檚 disease is defined by the aggregation of two proteins in the brain: amyloid plaques and tau tangles, both of which are known to be neurotoxic鈥� explains Joseph Therriault, a PhD student in the 91社区鈥檚 Integrated Program in Neuroscience under the supervision of Drs. Pedro Rosa-Neto and Serge Gauthier, Director of the Alzheimer Disease and Related Disorders Research Unit at the 91社区 Center for Studies in Aging. 鈥淎POE 隃�4 has been associated with amyloid plaques, but its association with tau tangles has been controversial. In our study of nearly 500 individuals, we demonstrate this association in living humans.鈥�

Therriault and his colleagues assessed two independent populations thanks to data available through the Translational Biomarkers in Aging and Dementia (TRIAD) cohort and the Alzheimer鈥檚 Disease Neuroimaging Initiative (ADNI), two research initiatives in which participating patients agreed to complete a variety of imaging and clinical assessments. In both instances, MRIs and PET scans were used to establish a relationship between APOE 隃�4 and tau tangles.

Tau tangles and memory

鈥淔or years, we have known that people with the APOE 隃�4 gene have more memory problems,鈥� adds Therriault, who is also the study鈥檚 lead author. 鈥淲e were able to show that carriers of this gene also had greater levels of tau tangles in memory centers of the brain, even after controlling for how much amyloid plaques they had.鈥�

While this study does not identify a biological mechanism for why this association exists, the findings contribute to an evolving framework in which APOE 隃�4 plays a central role in Alzheimer鈥檚 disease because of its role in both amyloid plaques and tau tangles.

Dr. Rosa-Neto adds that APOE 隃�4 has an important role in the very early stages of Alzheimer's disease. 鈥淭his paper highlights why APOE4 carriers show early memory deficits that eventually lead to dementia," he says.

鈥淥ur paper is an important step forward because we provide evidence that the substantial increased risk of developing dementia conferred by APOE 隃�4 genotype is related to both of the hallmark pathologies of Alzheimer鈥檚 disease,鈥� concludes Therriault.

The team next hopes to determine whether the studied individuals accumulate tau at a faster level through longitudinal imaging to see how subjects evolve over time.

Therriault, Rosa-Neto and Gauthier are hopeful that the research will help clinicians better assess the early signs of Alzheimer鈥檚 disease.

About this study

by Joseph Theriault et al. 聽was published in Journal of the American Medical Association: Neurology.

This work received financial support from the Canadian Institutes of Health Research, Fonds de la recherche en sant茅 du Qu茅bec聽and the Weston Brain Institute.聽

About 91社区

Founded in Montreal, Quebec, in 1821, 91社区 is Canada鈥檚 top ranked medical doctoral university. 91社区 is consistently ranked as one of the top universities, both nationally and internationally. It is a world-renowned institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. 91社区 attracts students from over 150 countries around the world, its 12,800 international students making up 31% per cent of the student body. Over half of 91社区 students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.