Original Research Article Dement Geriatr Cogn Disord 2004;18:189–196 DOI: 10.1159/000079200 Relation of Apolipoprotein(a) Size to Alzheimer’s Disease and Vascular Dementia Enzo Emanuele a Emmanouil Peros a,b Carmine Tomaino d Enrica Feudatari e Livia Bernardi d Giuliano Binetti e Raffaele Maletta d Giuseppe Micieli c Amalia C. Bruni d Diego Geroldi a,b a Molecular Medicine Laboratory, b Department of Internal Medicine and Medical Therapeutics, IRCCS Policlinico San Matteo, and c Department of Neurology, IRCCS Casimiro Mondino, University of Pavia, Pavia; d Regional Center of Neurogenetics, AS6, Lamezia Terme; e Memory Clinic and Neurobiology Laboratory, IRCCS Centro San Giovanni di Dio, FBF, Brescia, Italy Accepted: January 22, 2004 Published online: June 21, 2004 Diego Geroldi, MD Department of Internal Medicine and Medical Therapeutics IRCCS Policlinico San Matteo, University of Pavia Piazzale Golgi, 2, IT–27100 Pavia (Italy) Tel. +39 0382 502 568, Fax +39 0382 526 259, E-Mail d.geroldi@smatteo.pv.it ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2004 S. Karger AG, Basel 1420–8008/04/0182–0189$21.00/0 Accessible online at: www.karger.com/dem Key Words Lipoprotein(a) W Apolipoprotein(a) W Post-stroke dementia Abstract Lipoprotein(a) [Lp(a)] level is a newly established vascu- lar risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipopro- tein(a) [apo(a)] moiety. This suggests that the size poly- morphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer’s disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distri- bution of apo(a) phenotypes in groups of subjects con- sisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24–12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the posses- sion of at least one small-sized apo(a) isoform signifi- cantly increased the risk of AD to 1.92 (95% CI 1.02–3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associat- ed with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia. Copyright © 2004 S. Karger AG, Basel Introduction Ischemic cerebrovascular injury and Alzheimer’s dis- ease (AD) account for a large part of late-life health impairment [1, 2]. In addition, vascular dementia (VaD) has been increasingly recognised as an important cause of disability in the elderly [3]. Despite the heterogeneous nature of both AD and cerebrovascular accidents, lipo- protein and apolipoprotein abnormalities may be relevant in some phases of the natural history of both disorders. For instance, the possession of the Â4 allele of apolipopro- Downloaded by: Universita Studi Pavia 193.206.68.150 - 11/19/2014 11:10:32 AM