title: Multiplex assessment of a panel of 16 serum molecules for the differential diagnosis of Alzheimer's disease.
abstract: One of the current challenge in Alzheimer's disease (AD) is the identification of reliable biomarkers that might improve diagnostic accuracy, possibly correlating with the disease progression and patient's response to therapy. As the clinically validated AD biomarkers evaluate cerebrospinal fluid (CSF) parameters, the need for less invasive diagnostic markers is well evident. To this respect, blood circulating cytokines or growth factors have provided some encouraging results, even though no clinically validated to date. In 2007 Ray et al suggested a panel of 18 circulating molecules that might increase AD diagnostic accuracy. In an attempt of replicating their data, we designed a multiplex fluorimetric assay comprising 16 independent analytes and covering 15 out of the 18 described proteins. We collected serum samples from three diagnostic groups: probable AD (n=33), matched healthy controls (CNT, n=23) and non AD demented (NAD, n=14). After correction for age, we found an increased level of EGF-1 in AD in comparison to CNT and NAD, while an increase of TRAIL-R4 was found in NAD. However, evaluation of specificity/sensitivity by ROC curve analysis gave weak evidence of diagnostic accuracy (area under the curve = 0.63 and 0.66 for EGF and TRAIL-R4, respectively). Finally, we tried to find a diagnostic classifier by a multivariate algorithm. We found indication of diagnostic evidence for AD only, while NAD samples did not show a diagnostic pattern.
authors.affiliation: Department of Neuroscience, Istituto di Ricerche Famacologiche "Mario Negri"-IRCCS Milan, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Biella
authors.forename: Massimo
authors.initials: M
authors.lastname: Franceschi
authors.forename: Francesca
authors.initials: F
authors.lastname: De Rino
authors.forename: Annalisa
authors.initials: A
authors.lastname: Davin
authors.forename: Giacomo
authors.initials: G
authors.lastname: Giacalone
authors.forename: Paola
authors.initials: P
authors.lastname: Brambilla
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Bountris
authors.forename: Maria
authors.initials: M
authors.lastname: Haritou
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magnani
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
keywords: Alzheimer’s disease; EGF-1; artificial neural networks; diagnosis; machine learning; multiplex analysis; multivariate classifier; peripheral biomarkers