Apolipoprotein E (APOE) polymorphism in£uences serum APOE levels in Alzheimer’s disease patients and centenarians Francesco Panza, CA Vincenzo Solfrizzi, Anna M. Colacicco, Anna M. Basile, Alessia D’Introno, Cristiano Capurso, Maria Sabba, Sabrina Capurso and Antonio Capurso Department of Geriatrics,Center for Aging Brain, Memory Unit,University of Bari, Policlinico, Piazza Giulio Cesare,11-70124 Bari, Italy CA Corresponding Author: geriat.dot@geriatria.uniba.it Received15 January 2003; accepted 29 January 2003 DOI:10.1097/01.wnr.0000063660.48571.78 Vascular factors may play a role in the etiology of Alzheimer’s dis- ease (AD) and increased serum apolipoprotein E (APOE) levels in AD couldbe ofinterest,asAPOEconcentrationis associatedwith vascular disease. Aims of this study were to evaluate the in£uence of APOE genotype on serum APOE levels, and, secondly, to study serum APOE concentrations in relation to age and AD. APOE gen- otypes, serum total cholesterol, LDL cholesterol, HDL cholester- ol, total cholesterol/HDL cholesterol ratio, triglycerides, and serum APOE were performed on 52 healthy centenarians, 49 AD patients, 45 age-matched controls, and 72 young healthy adults. In allstudypopulationa signi¢canttrendinreductionofserumAPOE levelsfromAPOE E2-to E4carrierswasobserved.Thedi¡erencein serum APOE levels among age groups signi¢cantly decreased in E4 carriers only, including HDL cholesterol; no signi¢cant di¡erences between AD patients and age-matched controls were found. In these highly selected populations, APOE genotype distribution stronglyin£uences serum APOE concentration, not suggesting, at present, a possible role as a biochemical marker for AD, but only as a putative longevity factor. NeuroReport 14:605^608  c 2003 Lippincott Williams & Wilkins. Key words: Alzheimer’s disease; Apolipoprotein E genotype; Centenarians; Longevity; Serum apolipoprotein E INTRODUCTION Apolipoprotein E (APOE) is a polymorphic protein involved in transport and redistribution of lipids in various tissues. Three major APOE isoforms, E2, E3, and E4, which are coded by the alleles E2, E3, and E4 at a single locus on chromosome 19, have been identified. The APOE E4 allele is associated with high serum total cholesterol (TC), low- density lipoprotein (LDL) cholesterol, and apolipoprotein B levels in many populations [1], and has been found to increase risk for coronary artery disease (CAD) and myocardial infarction [2]. Several studies have also shown that APOE E4 allele is the strongest risk factor for sporadic and familial late-onset Alzheimer’s disease (AD) [3]. Further, a significantly diminished prevalence of the APOE E4 allele in centenarians has been observed [4,5]. Finally, physiological serum APOE concentrations, which vary from 30 to 250 mg/l [6], have been shown to modulate lipid metabolism [7], suggesting that APOE concentration, in addition to APOE polymorphism, might be a risk factor for CAD and cerebrovascular disease (CVD) [6,8]. Interestingly, increased serum APOE levels have been observed in early- and late-onset AD patients compared with controls [8], supporting the growing evidence that vascular factors play a role in the etiology of AD. In this study, we analyzed the relationship between serum APOE concentrations and APOE polymorphism in AD patients, and age-matched healthy controls, centenarians, and young healthy adults. In these populations, differences in serum APOE levels have been evaluated in relation to age and AD. SUBJECTS AND METHODS Fifty-two centenarians, 49 AD patients, and 117 healthy subjects (45 age-matched controls and 72 young adults), unrelated caregivers (spouses, friends or neighbors) or volunteers, were evaluated in the Centre for Aging Brain, Memory Unit, Department of Geriatrics, University Hospi- tal, Bari, Italy, between November 1997 and March 1999. Centenarians were recruited from all over Apulia region (Southern Italy), at their home, by Central Population Register. The AD group included 49 patients with sporadic disease. Clinical diagnosis of probable AD was performed according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association criteria [10]. The ascertainment, diagnosis and collection of cases, centenarians and controls has been described in detail elsewhere [5,11]. The four groups of the present study had 0959-4965  c Lippincott Williams & Wilkins Vol 14 No 4 24 March 2003 605 MOTOR SYSTEMS NEUROREPORT Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.