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

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

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

Abstract

Background: Apolipoprotein(a) [apo(a)], the distinctive, highly polymorphic glycoprotein of lipoprotein(a), shares a series of common features with apolipoprotein E (apoE), which is implicated in the development of Alzheimer disease.

Objective: To determine whether apo(a) is associated with Alzheimer disease.

Design: Case-control study.

Setting: University hospitals in Europe.

Participants: 285 patients with Alzheimer disease and 296 controls.

Measurements: Plasma lipoprotein(a) levels, size of the apo(a) isoforms, and apoE and apo(a) genotyping.

Results: Among carriers of the apoE ε4 allele, lipoprotein(a) was associated with a progressive, age-dependent increased risk for late-onset Alzheimer disease (odds ratio for patients >80 years of age, 6.0 [95% CI, 1.2 to 30.8]; P < 0.01). Among noncarriers older than 80 years of age, lipoprotein(a) was associated with a reduced risk for Alzheimer disease (odds ratio, 0.4 [CI, 0.2 to 0.9]; P < 0.05).

Conclusions: In this convenience sample, lipoprotein(a) was an additional risk factor for late-onset Alzheimer disease in carriers of the apoE ε4 allele. However, lipoprotein(a) may protect against late-onset Alzheimer disease in noncarriers.

Article and Author Information

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{at}hola.hospvd.ch.
Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}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.