© J. Poirier 2025-2026
Recent Publications
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 (Proc. Natl. Acad. Sci. 87:303). 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: 1091, J.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: 500, J. Neurochem. 66:2410, J. Neurochem. 70:1466, Neuroscience 373: 20-
36, JAMA Neurol. 75 (5) 608-619, Nature Comm., 10 (1) 2240-2255, Nature Mol. Psychiatry 26, 5977–5988.
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, J. Alz. Dis 54: 913-922, these keys contributions to canadian translation research effort was recognized by the
Galien 1996 Prize and, the Genesis Award 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: 39, Trends Mol. Medicine 9:94, Neurobiol. Aging 35 (2) 3-10), 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.
CSF Biomarkers of AD Progression in “at risk” Asymptomatic Subjects: Combining genomic information (GWAS, eQTL),
multiple cohort analyses and new sensitive bioassays (OLINK, LC/MS /MS, SimoA, Somascan, Nulisa and Luminex), we successfully
documented a series of novel CNS biomarkers and genetic risk factors that modulate AD pathology in the pre-symptomatic phase of AD
(JAMA Neurol. 75:5:608-619, Alzheimer & Dementia 14:787-796, Nature Comm.10:2240-2255, Alzheimer and Dementia 15:
742-753, Nature Communication 12: 53, JAMA Neurol. 79 (3) 228-243, JAMA Neurol. 79(10):1025-1035, Alzheimer and
Dementia 19, 7: 2816-2830, Alzheimer and Dementia 19: 12, 5620-5631, Brain 147:5, 1680-1695, Nature Scientific Reports 14:
14718, J. Lipid Res. (2024) 65(11) 100667, Alzheimer and Dementia DOI:10.1002/alz.14065).
mRNAs involved in synaptic remodelling in the injured adult rodent brain (Proc. Natl. Acad. Sci. 87:303). 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: 1091, J.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: 500, J. Neurochem. 66:2410, J. Neurochem. 70:1466, Neuroscience 373: 20-
36, JAMA Neurol. 75 (5) 608-619, Nature Comm., 10 (1) 2240-2255, Nature Mol. Psychiatry 26, 5977–5988.
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, J. Alz. Dis 54: 913-922, these keys contributions to canadian translation research effort was recognized by the
Galien 1996 Prize and, the Genesis Award 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: 39, Trends Mol. Medicine 9:94, Neurobiol. Aging 35 (2) 3-10), 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.
CSF Biomarkers of AD Progression in “at risk” Asymptomatic Subjects: Combining genomic information (GWAS, eQTL),
multiple cohort analyses and new sensitive bioassays (OLINK, LC/MS /MS, SimoA, Somascan, Nulisa and Luminex), we successfully
documented a series of novel CNS biomarkers and genetic risk factors that modulate AD pathology in the pre-symptomatic phase of AD
(JAMA Neurol. 75:5:608-619, Alzheimer & Dementia 14:787-796, Nature Comm.10:2240-2255, Alzheimer and Dementia 15:
742-753, Nature Communication 12: 53, JAMA Neurol. 79 (3) 228-243, JAMA Neurol. 79(10):1025-1035, Alzheimer and
Dementia 19, 7: 2816-2830, Alzheimer and Dementia 19: 12, 5620-5631, Brain 147:5, 1680-1695, Nature Scientific Reports 14:
14718, J. Lipid Res. (2024) 65(11) 100667, Alzheimer and Dementia DOI:10.1002/alz.14065).
