Galanin and α-MSH autoantibodies in cerebrospinal fluid of patients with Alzheimer's disease

Background: Neuropeptides galanin and alpha-melanocyte-stimulating hormone (alpha-MSH) are involved in the regulation of memory and appetite. Increased galanin and decreased alpha-MSH levels were reported in postmortem brains of patients with Alzheimer's disease (AD) but the underlying mechanisms are uncertain. Here we studied if autoantibodies (autoAbs) reacting with galanin and alpha-MSH are altered in AD. Methods: Levels of free and total IgG autoAbs reacting with galanin and alpha-MSH were measured in sera and cerebrospinal fluid (CSF) of 18 subjects with AD and in 15 age-matched non-demented controls. Values were correlated with Mini-Mental State Examination (MMSE) score, body mass index (BMI) and CSF levels of AD biomarkers. Results: CSF levels of total but not free IgG autoAbs against galanin were increased in AD, resulting in increased percentage of galanin autoAbs present as immune complexes. CSF levels of galanin total autoAbs and a-MSH free autoAbs correlated negatively with the severity of cognitive impairment as measured by MMSE. Both total and free autoAbs against galanin and alpha-MSH in CSF correlated negatively with age in AD patients but not in controls. CSF levels of galanin autoAbs and free alpha-MSH AutoAbs negatively correlated with CSF levels of t-Tau, p-Tau and ratios of t-Tau/A beta 42 or p-Tau/A beta 42 in AD patients but not in controls. Conclusions: AutoAbs reacting with galanin and alpha-MSH are present in CSF and are associated with clinical characteristics of AD patients. The functional significance and therapeutic potential of these autoAbs should be further clarified. (C) 2011 Elsevier B.V. All rights reserved.