Distinct Effects of Testosterone on Plasma and Cerebrospinal Fluid Amyloid-β Levels

Article type: Research Article

Authors: Wahjoepramono, Eka J.^{a; b; 1} | Wijaya, Linda K.^{a; b; c; 1} | Taddei, Kevin^{a; c} | Martins, Georgia^{a; c} | Howard, Matthew^{a; c} | de Ruyck, Karl^{a; c} | Bates, Kristyn^{a; c} | Dhaliwal, Satvinder S.^d | Verdile, Giuseppe^{a; c} | Carruthers, Malcolm^e | Martins, Ralph N.^{a; c; *}

Affiliations: [a] Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia | [b] Medical Faculty, Pelita Harapan University – Neuroscience Centre, Siloam Gleneagles Hospital, Lippo Karawaci, Tangerang, Indonesia | [c] Sir James McCusker Alzheimer's Disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Hollywood Private Hospital, Nedlands, WA, Australia | [d] School of Public Health, Curtin University of Technology, Bentley, WA, Australia | [e] Centre of Men's Health, London, UK

Correspondence: [*] Corresponding author: Prof. Ralph N. Martins, Edith Cowan University, 100 Joondalup Drive (Building 17), Joondalup, WA 6027, Australia. Tel.: +1 61 8 6304 5456; Fax: +1 61 8 6304 5851; E-mail: [email protected].

Note: [1] Both authors contributed equally.

Abstract: The effect of testosterone on the levels of the Alzheimer's disease amyloid-β peptide (Aβ) was investigated in guinea pigs. Castrated guinea pigs (GPX) were administered testosterone at two different dosages, following which plasma and cerebrospinal fluid (CSF) Aβ40 levels were measured. Plasma Aβ40 levels were reduced in GPX in the early stages of low-dose testosterone treatment, whereas CSF Aβ40 levels were only reduced by the time circulating testosterone had returned to untreated GPX levels. The supraphysiological testosterone dose did not reduce CSF Aβ40 levels significantly until circulating testosterone was back to uncastrated levels, whereas plasma Aβ40 levels significantly increased over time in these animals. These results indicate that the extent of testosterone-induced changes to Aβ40 levels and their response rates depend on both the tissue examined and testosterone dosage.

Keywords: Aging, Alzheimer's disease, amyloid-β, castration, cerebrospinal fluid, guinea pig, testosterone

DOI: 10.3233/JAD-2008-15111

Journal: Journal of Alzheimer's Disease, vol. 15, no. 1, pp. 129-137, 2008