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

  • J. Poirier
  • P. Sévigny
Part of the Journal of Neural Transmission. Supplementa book series (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.

Keywords

apoE4 Allele ChAT Activity Nicotinic Binding apoE Knockout Mouse Allele Copy Number 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • J. Poirier
    • 1
    • 3
  • P. Sévigny
    • 2
  1. 1.McGill Centre for Studies in Aging, Douglas Hospital Research Centre, Department of Psychiatry, Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  2. 2.Nova Molecular Inc.MontrealCanada
  3. 3.McGill Centre for Studies in Aging, Douglas Hospital Research CentreVerdunCanada

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