title: Plasma gelsolin is decreased and correlates with rate of decline in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder where definite diagnosis can only be made postmortem, and for which the most promising peripheral markers of disease state and severity have been found in the cerebrospinal fluid. However, recent results suggest that differences in the levels of certain plasma proteins do exist between AD patients and non-demented controls (NDC). Herein, we undertook an untargeted discovery study using isobaric mass tagging to compare the plasma protein levels between slow cognitive declining AD patients, rapid cognitive declining AD patients (RCD) and NDC subjects. Subsequent relative quantification and statistical analysis identified a list of candidate proteins able to distinguish RCD from NDC groups based on multivariate analysis. Selected proteins were then validated by western blot analysis in an independent sample set of 60 AD and 35 NDC subjects. In this cohort, AD patients displayed significantly lower plasma gelsolin levels compared to NDC subjects. Additionally, gelsolin levels correlated with disease progression rate estimated by Mini-Mental Status Examination decline per year. In order to further investigate gelsolin expression, three different brain regions from an additional cohort of 23 subjects and their respective plasma samples were analysed. No significant change in brain gelsolin levels could be established between AD and control subjects. Interestingly, this study reveals yet another condition where plasma gelsolin levels are decreased and our findings, together with the reported interaction of gelsolin and amyloid-beta, makes plasma gelsolin an attractive candidate for further studies targeted at better understanding disease progression in AD.
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Güntert
authors.forename: James
authors.initials: J
authors.lastname: Campbell
authors.forename: Muzamil
authors.initials: M
authors.lastname: Saleem
authors.forename: Darragh P
authors.initials: DP
authors.lastname: O'Brien
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Helen L
authors.initials: HL
authors.lastname: Byers
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Ward
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D018260:Gelsolin / Q000097:blood*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D001798:Blood Proteins; D018260:Gelsolin