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Interactions between Apolipoprotein E and Apolipoprotein(a) in Patients with Late-Onset Alzheimer Disease

Vincent Mooser, MD; Nicole Helbecque, PhD; Judit Miklossy, MD; Santica M. Marcovina, PhD; Pascal Nicod, MD; and Philippe Amouyel, MD, PhD
[+] Article and Author Information

From CHUV University Hospital, Lausanne, Switzerland; Institut Pasteur de Lille, Lille, France; and University of Washington, Seattle, Washington.


Acknowledgments: The authors thank Valérie Codron, Pushpa Darekar, Nathalie Fiévet, Vincent Lenain, Sandra Testuz, and Talmadge Trammell for their excellent technical assistance. They also thank Stefan Catsicas, Dominique Cottel, Roger Darioli, Helen Hobbs, Geneviève Leuba, Pierre Magistretti, and Gérard Waeber for helpful discussions.

Grant Support: By the Swiss Foundation for Scientific Research (32-44471.95), the Placide Nicod and Octave Botnar Foundations, Servier Laboratory, Fondation de la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale, and Institut Pasteur de Lille.

Requests for Single Reprints: Vincent Mooser, MD, Department of Medicine, BH 19-135, CH-1011, CHUV University Hospital, Lausanne, Switzerland; e-mail, vincent.mooser@hola.hospvd.ch.

Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints@mail.acponline.org.

Current Author Addresses: Drs. Mooser and Nicod: Department of Medicine, BH 19-135, CH-1011 CHUV Lausanne, Switzerland.

Drs. Helbecque and Amouyel: Institut National de la Santé et de la Recherche Médicale U 508, Institut Pasteur de Lille, F-59019 Lille Cedex, France.

Dr. Miklossy: Department of Pathology, Rue du Bugnon, CH-1011 CHUV Lausanne, Switzerland.

Dr. Marcovina: University of Washington, Northwest Lipid Research Laboratories, 2121 North 35th Street, Seattle, WA 98103.

Author Contributions: Conception and design: V. Mooser, N. Helbecque, P. Nicod, P. Amouyel.

Analysis and interpretation of the data: V. Mooser, N. Helbecque, J. Miklossy, P. Amouyel.

Drafting of the article: V. Mooser.

Critical revision of the article for important intellectual content: V. Mooser, N. Helbecque, S. Marcovina, J. Miklossy, P. Nicod, P. Amouyel.

Final approval of the article: V. Mooser, N. Helbecque, J. Miklossy, S.M. Marcovina, P. Nicod, P. Amouyel.

Provision of study materials or patients: V. Mooser, N. Helbecque, J. Miklossy, S.M. Marcovina, P. Amouyel.

Statistical expertise: V. Mooser, N. Helbecque, P. Amouyel.

Obtaining of funding: V. Mooser, P. Nicod, P. Amouyel.

Administrative, technical, or logistic support: V. Mooser, N. Helbecque, J. Miklossy, S.M. Marcovina, P. Nicod, P. Amouyel.

Collection and assembly of data: V. Mooser, N. Helbecque, J. Miklossy, P. Amouyel.


Ann Intern Med. 2000;132(7):533-537. doi:10.7326/0003-4819-132-7-200004040-00004
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The apolipoprotein E (apoE) E4 isoform has been implicated in the pathogenesis of Alzheimer disease (1). Not all carriers of the apoE ε4 allele develop Alzheimer disease; therefore, additional risk factors probably exist (2). The very-low-density lipoprotein receptor (3) and the low-density lipoprotein receptor-related protein (4) (a receptor that is expressed by human neurons and internalizes apoE [5]) have been associated with Alzheimer disease and with defects in neuronal migration (6).

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Figure.
Proposed model for the dual, apolipoprotein E (apoE) genotype-dependent association between lipoprotein(a) and Alzheimer diseaseAD). Left.HSPGLRPRight.

( Absorption of apoE in the absence of apolipoprotein(a) [apo(a)]. ApoE-containing lipoproteins bind heparan sulfate proteoglycans ( ) and low-density lipoprotein receptor-related protein ( ) to be internalized in the neuron. Once internalized, apoE E2/3 isoforms have a protective effect; the apoE E4 isoform has the opposite effect. Absorption of apoE in the presence of apo(a). Lipoproteins that contain both apoE and apo(a) bind to the cell surface with a higher affinity than those that contain only apoE, and a larger fraction of apoE is internalized in the cell. In persons without the apoE ε4 allele, the increased amount of apoE in the cell contributes to better protection; in carriers of this allele, neurons have a higher risk for degeneration. Small circles represent kringles of apo(a); triangles represent apoE; large circles represent apoE-containing lipoproteins.

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Summary for Patients

Alzheimer Disease, Apolipoprotein E, and Apolipoprotein(a)

The summary below is from the full report titled “Interactions between Apolipoprotein E and Apolipoprotein(a) in Patients with Late-Onset Alzheimer Disease.”. It is in the 4 April 2000 issue of Annals of Internal Medicine (volume 132, pages 533-537). The authors are V. Mooser, N. Helbecque, J. Miklossy, S.M. Marcovina, P. Nicod, and P. Amouyel.

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