Association of Cardiovascular Factors and Alzheimer's Disease Plasma Amyloid-β Protein in Subjective Memory Complainers

Article type: Research Article

Authors: Bates, Kristyn A.^{a; b; c} | Sohrabi, Hamid R.^{b; c} | Rodrigues, Mark^{a; b} | Beilby, John^d | Dhaliwal, Satvinder S.^e | Taddei, Kevin^{a; b; c} | Criddle, Arthur^f | Wraith, Megan^f | Howard, Matthew^{a; b; c} | Martins, Georgia^{a; b; c} | Paton, Athena^{b; c} | Mehta, Pankaj^g | Foster, Jonathan K.^{a; b} | Martins, Ian J.^{a; b; c} | Lautenschlager, Nicola T.^{c; h; i} | Mastaglia, Frank L.^j | Laws, Simon M.^{a; b; k} | Gandy, Samuel E.^l | Martins, Ralph N.^{a; b; c; *}

Affiliations: [a] School of Exercise Biomedical and Health Science, Edith Cowan University, Joondalup, WA, Australia | [b] Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Nedlands, WA, Australia | [c] School of Psychiatry and Clinical Neuroscience, University of Western Australia, Crawley, WA, Australia | [d] Western Australian Centre for Pathology and Medical Research and the University of Western Australia, Crawley, WA, Australia | [e] School of Public Health, Curtin University of Technology, Perth, WA, Australia | [f] Western Medicine, Hollywood Specialist Centre, Nedlands, WA, Australia | [g] Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA | [h] Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Normanby House, St George's Hospital, Kew, VIC, Australia | [i] West Australian Centre for Health and Ageing, University of Western Australia, Crawley, WA, Australia | [j] Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Queen Elizabeth II Medical Centre, Crawley, WA, Australia | [k] Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technische Universitat Munchen (TU-Munchen), Munchen, Germany | [l] Mount Sinai School of Medicine, New York, NY, USA

Correspondence: [*] Corresponding author: Prof. Ralph N. Martins, School of Exercise, Biomedical and Health Science, Edith Cowan University, 270 Joondalup Dr, Joondalup, WA 6027, Australia. Tel.: +61 08 6304 5456; Fax: +61 08 6304 5851; E-mail: [email protected].

Abstract: A strong link is indicated between cardiovascular disease (CVD) and risk for developing Alzheimer's disease (AD), which may be exacerbated by the major AD genetic risk factor apolipoprotein Eε4 (APOEε4). Since subjective memory complaint (SMC) may potentially be an early indicator for cognitive decline, we examined CVD risk factors in a cohort of SMC. As amyloid-ε (Aβ) is considered to play a central role in AD, we hypothesized that the CVD risk profile (increased LDL, reduced HDL, and increased body fat) would be associated with plasma Aβ levels. We explored this in 198 individuals with and without SMC (average age = 63 years). Correlations between Aβ40 and HDL were observed, which were stronger in non-APOEε4 carriers (rho = −0.315, p < 0.001) and in SMC (rho = −0.322, p = 0.01). There was no relationship between percentage body fat and Aβ40 in this cohort. Age and HDL remained predictive for plasma Aβ40 using multivariate regression analysis. We report a novel negative association between HDL and Aβ, which if demonstrated to be causal has implications for the development of lifestyle interventions and/or novel therapeutics. The relationship between HDL and Aβ and the potential significance of such an association needs to be validated in a larger longitudinal study.

Keywords: Aging, amyloid-β, apolipoprotein E, cholesterol, dementia, high density lipoprotein

DOI: 10.3233/JAD-2009-1050

Journal: Journal of Alzheimer's Disease, vol. 17, no. 2, pp. 305-318, 2009