Increased Cerebrospinal Fluid Level of Insulin-like Growth Factor-II in Male Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Åberg, Daniel^a | Johansson, Per^{a; b} | Isgaard, Jörgen^{a; c} | Wallin, Anders^d | Johansson, Jan-Ove^a | Andreasson, Ulf^d | Blennow, Kaj^d | Zetterberg, Henrik^{d; e} | Åberg, N. David^a | Svensson, Johan^{a; f; *}

Affiliations: [a] Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden | [b] Department of Neuropsychiatry, Skaraborg Hospital, Falköping, Sweden | [c] School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, NSW, Australia | [d] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden | [e] UCL Institute of Neurology, Queen Square, London, UK | [f] Department of Endocrinology, Skaraborg Hospital, Skövde, Sweden

Correspondence: [*] Correspondence to: Dr. Johan Svensson, Department of Internal Medicine, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. Tel.: +46 31 7411712; Fax: +46 31 821524; [email protected]

Abstract: Background: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer’s disease (AD). Objective and methods: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). Results: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p <  0.01 and p <  0.05, respectively). Furthermore, CSF IGFBP-2 level was increased in AD men versus SMCI men (p <  0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. Conclusion: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.

Keywords: Alzheimer’s disease, biomarker, cerebrospinal fluid, IGF-II, IGFBP-1, IGFBP-2, mild cognitive impairment

DOI: 10.3233/JAD-150351

Journal: Journal of Alzheimer's Disease, vol. 48, no. 3, pp. 637-646, 2015