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Le noyeau de l’équipe et les publications récentes
Brain Reinnervation and Apolipoprotein E Neurobiology: The initial phase of our research program has been to identify key  mRNAs involved in synaptic remodelling in the injured adult rodent brain. In an article published in Proc. Natl. Acad. Sci. 87:303, we  documented the fact that a limited numbers of mRNAs of moderate prevalence exhibit significant induction during the active phase of  reinnervation in the experimentally deafferented rat hippocampus (a partial model of Alzheimer's disease pathology). The most  important transcript identified during follow-up cDNA screenings turned out to be a protein known as apolipoprotein E (apoE), a  well-characterized cholesterol transporter produced locally in the brain.  Apolipoprotein E4 and the Pathophysiology of Alzheimer’s disease: In a follow-up series of studies in neurodegenerative diseases,  we published a breakthrough report in the Lancet 342: 697 where we reported that sporadic cases with Alzheimer's disease (AD)  exhibit an abnormally high incidence of a normally rare apoE allele referred to as the apoE4. Follow-up publications by our team  demonstrated a potent apoE4-gene dose effect on : a) age of onset, b) rate of progression, c) risk of developing the disease and more  importantly, d) on the cholinergic status and integrity in the brain of sporadic Alzheimer’s disease subjects:   Proc. Natl. Acad. Sci. 92: 12260,  Lancet  347: 1091J.A.M.A. 278: 1349, Proc. Natl. Acad. Sci. 98: 10966.    Apolipoprotein E influences the Beta-Amyloid Neurotoxicity and Metabolism: In more recent years, we uncovered the biological  connection linking the so-called beta amyloid cascade hypothesis of AD and apolipoprotein E metabolism in the pathophysiology of  Alzheimer’s disease. Using various techniques, models and approaches, we documented the apoE/beta amyloid relationship in vitro  and in vivo. The studies were published in Nature  387: 500J. Neurochem.  66:2410, J. Neurochem.  70:1466, Brain Research  Reviews 27: 199  Apolipoprotein E4: A Pharmacogenomic Marker of Drug Efficacy in Alzheimer’s disease: Our modest but significant  contribution to the emerging field of the pharmacogenomics prompted several pharmaceutical corporations (Eli Lilly, Bayer, Parke  Davis, Novartis and Smith Kline Beecham) to re-evaluate their clinical drug trial designs to include an apoE genotype arm. We and  others have documented on multiple occasions the fact that the efficacy of several memory enhancers (especially cholinomimetics) are  highly dependent upon the individual’s apoE or BuChE K genotypes Proc. Natl. Acad. Sci.  92: 12260, Neurology 50: 669, Curr.  Pharmacogen. 8: 63 this key contribution to canadian translation research effort was recognized by the Galien 1996 Prize and Genesis  Awards 2010 Cholesterol Metabolism as Therapeutic Target for the Treatment of Alzheimer’s Disease: As early as 1993, we proposed that the  reduction in apoE concentrations reported in the blood and brain of apoE4 allele carriers could be alleviated by drugs that specifically  promote apoE synthesis and secretion in the CNS. Building on the approach, we identified three different agents (out of several  hundreds) with strong apoE inducing capacity: estrogen, indomethacin and probucol (Eur. J. Neurosci. 18: 1, Neuroscience 121: 99     Alz. Dem.  4: 591, Curr Alz Res 5:33). Independently of this work, these three compounds had been shown to reduce the risk of  developing AD in several epidemiological studies ran in the US, Europe and Asia. As a consequence, we choose to focus on the drug  Probucol, a potent cholesterol-lowering agent for efficacy and safety reasons. In a small proof-of-principal study performed in  Montreal (Adv. Behav. Biol. 51: 39Trends Mol. Medicine 9:94, Neurobiol. Aging 35 (2) 3), we discovered that a 6-month  treatment with Probucol in mild-tomoderate AD stopped disease progression in the majority of the 12 patients enrolled in the study and  “improved” the activities of daily living for the entire group. As of the spring of 2017, we are now preparing the second phase of a  three part clinical program evaluating the potential benefits of probucol treatment in the prevention of sporadic Alzheimer’s disease in  healthy control subjects with a parental history of AD.   
Franšais Franšais Team publications