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Apolipoprotein E4, cholinergic integrity and the pharmacogenetics of Alzheimer’s disease

  • Conference paper
Ageing and Dementia

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURAL SUPPL,volume 53))

Summary

Recent evidence indicates that apolipoprotein E (apoE) plays a central role in the brain’s response to injury. The coordinated expression of apoE and its receptors (the so-called LDL receptor family) appears to regulate the transport and internalization of cholesterol and phospholipids during the early phase of the reinnervation process in the adult brain. During dendritic remodelling and synaptogenesis, neurons progressively repress the synthesis of cholesterol in favor of cholesterol internalization through the apoE/LDL receptor pathway. The discovery a few years ago that the apolipoprotein E4 allele found normal in 15% of the normal population is strongly linked to both sporadic and familial late onset Alzheimer’s disease (AD) raises the possibility that a dysfunction of the lipid transport system associated with compensatory sprouting and synaptic remodelling could be central to the AD process. The role of apoE in the CNS is particularly important in relation to cholinergic system which relies to a certain extent on the integrity of phospho-lipid homeostasis in neurons. Recent evidence obtained in our laboratory indicates that apoɛ4 allele has a direct impact on cholinergic system activity in the brain as well as on drug efficacy profile in AD subjects treated with cholinomimetic agents.

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Abbreviations

ACh:

acetylcholine

AchE:

Acetylcholine esterase

AD:

Alzheimer’s disease

apoE:

apolipoprotein E

ChAT:

choline acetyltransferase

PC:

phosphatidylcholine

PE:

phosphatidyl ethanolamine

NBM:

Nucleus basalis of Meynert

DBB:

diagonal band of Broca

GFAP:

glial fibrillary acidic protein

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Author information

Authors and Affiliations

  1. McGill Centre for Studies in Aging, Douglas Hospital Research Centre, Department of Psychiatry, Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada

    J. Poirier

  2. Nova Molecular Inc., Montreal, Québec, Canada

    P. Sévigny

  3. McGill Centre for Studies in Aging, Douglas Hospital Research Centre, H4H 1R3, 6875 LaSalle Blvd, Verdun, Québec, Canada

    J. Poirier

Authors
  1. J. Poirier
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  2. P. Sévigny
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Editor information

Editors and Affiliations

  1. Ludwig-Boltzmann-Institut für Klinische Neurobiologie, Wien, Österreich, Austria

    K. Jellinger (Prof. Dr.) (Prof. Dr.)

  2. Universitätsklinik für Neurologie, Graz, Österreich, Austria

    F. Fazekas (Prof. Dr.) (Prof. Dr.)

  3. Institut für Experimentelle Pharmakologie, Forschungsinitiative EBEWE, Graz, Österreich, Austria

    M. Windisch (Dr.) (Dr.)

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© 1998 Springer-Verlag Wien

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Poirier, J., Sévigny, P. (1998). Apolipoprotein E4, cholinergic integrity and the pharmacogenetics of Alzheimer’s disease. In: Jellinger, K., Fazekas, F., Windisch, M. (eds) Ageing and Dementia. Journal of Neural Transmission. Supplementa, vol 53. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6467-9_18

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  • DOI: https://doi.org/10.1007/978-3-7091-6467-9_18

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83114-4

  • Online ISBN: 978-3-7091-6467-9

  • eBook Packages: Springer Book Archive

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