Affiliations: [a] Department of Clinical Biochemistry and Immunology, Royal Sussex County Hospital, Brighton, UK | [b] Cognitive Treatment and Research Unit, Sussex Partnership NHS Foundation Trust, Uckfield, East Sussex, UK | [c] Institute of Postgraduate Medicine, Brighton & Sussex Medical School, University of Brighton, Falmer, Brighton, UK
Correspondence:
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Correspondence to: Edward R. Smith, Department of Clinical Biochemistry and Immunology, Royal Sussex County Hospital, Eastern Road, Brighton, BN2 5BE, UK. Tel.: +44 1273 696955; Fax: +44 1273 664828; E-mail: [email protected].
Abstract: The significance of vascular risk factors in the development and progression of Alzheimer's disease (AD) is now widely recognized. Fetuin-A is an abundant plasma protein that predicts vascular risk in a variety of clinical settings. In the context of cerebral ischemia, fetuin-A appears to be anti-inflammatory. Given the apparent importance of neuroinflammation in cognitive decline, we analyzed fetuin-A concentrations and pro-inflammatory cytokine levels in a cohort of 34 patients with mild-to-moderate AD, and compared these to age-matched controls. Further, we analyzed the relationship between plasma fetuin-A concentration and a measure of cognitive impairment using multivariate regression modeling. Plasma fetuin-A concentrations were lower in the patient group (p = 0.006) compared with controls and were significantly correlated with Mini-Mental State Examination (MMSE) score (r = 0.504, p = 0.002). Fetuin-A concentration was also significantly and inversely correlated with plasma TNF-α concentration (r = −0.496, p = 0.003). The association between MMSE performance and fetuin-A was maintained even after multivariate adjustment for other risk factors including TNF-α (adjusted R2 total = 0.371). Using this model, plasma fetuin-A concentration explained 21% of the variance in MMSE scores. Further studies are needed to evaluate whether fetuin-A is related to the progression and pathogenesis of AD.
