Association of Plasma Aβ₄₀ Peptides, But Not Aβ₄₂, with Coronary Artery Disease and Diabetes Mellitus

Article type: Research Article

Authors: Roeben, Benjamin^{a; b; *} | Maetzler, Walter^{a; b; i} | Vanmechelen, Eugeen^{c; d} | Schulte, Claudia^{a; b} | Heinzel, Sebastian^{a; b} | Stellos, Konstantinos^{e; f; g} | Godau, Jana^a | Huber, Heiko^{a; b; h} | Brockmann, Kathrin^{a; b} | Wurster, Isabel^{a; b} | Gaenslen, Alexandra^{a; b} | Grüner, Eva^a | Niebler, Raphael^{h; i} | Eschweiler, Gerhard W.^{h; i} | Berg, Daniela^{a; b} | the TREND study team^a

Affiliations: [a] Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany | [b] German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany | [c] Key4AD, Eke, Belgium | [d] Innogenetics N.V. (now Fujirebio Europe N.V.), Ghent, Belgium | [e] Institute of Cardiovascular Regeneration, Centre of Molecular Medicine, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany | [f] Department of Cardiology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany | [g] German Center of Cardiovascular Research (DZHK), Frankfurt, Germany | [h] Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany | [i] Geriatric Center, University of Tübingen, Tübingen, Germany

Correspondence: [*] Correspondence to: Benjamin Roeben, MD, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. Tel.: +49 7071 29 82 34 0; Fax: +49 7071 29 44 09; E-mail: [email protected].

Abstract: Background/Objective: Plasma levels of amyloid-beta (Aβ) 1-40 peptide have been proposed to be associated with cardiovascular mortality in patients with coronary artery disease (CAD). Therefore, we aimed to investigate the association of plasma Aβ levels with CAD, cardiovascular risk factors (CVRF), and APOE genotype in non-demented elderly individuals. Methods: Plasma Aβ1 - 40 and Aβ1 - 42 levels of 526 individuals (mean age of 63.0±7.3 years) were quantified with the INNO-BIA plasma Aβ forms assay based on multiplextrademark technique. APOE genotype was determined with an established protocol. Presence of CAD and CVRFs were ascertained using a questionnaire and/or medical records. Results: Plasma Aβ1 - 40 levels were significantly higher in individuals with CAD (p = 0.043) and, independently, in individuals with diabetes mellitus (DM) type 2 (p = 0.001) while accounting for age- and gender-effects. Plasma Aβ1 - 42 levels were higher in APOE ɛ4 carriers (p = 0.004), but were neither relevantly associated with CAD nor with any CVRF. Plasma Aβ1 - 40 showed no association with APOE genotype. Discussion: Our findings argue for an association of circulating plasma Aβ1 - 40 peptides with incident CAD and DM. Further investigations are needed to entangle the role of Aβ1 - 40 role in the pathophysiology of cardiovascular disease independent of its known role in Alzheimer’s disease.

Keywords: Alzheimer’s disease, amyloid-beta, APOE genotype, coronary artery disease, diabetes mellitus, vascular

DOI: 10.3233/JAD-150575

Journal: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 161-169, 2016