title: Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease.
abstract: The link between biometals and Alzheimer's disease (AD) has been investigated with a focus on local metal accumulations. In this work, we have looked at systemic metal changes and computed a score (M-score) based on metal disarrangements to discriminate patients with AD from patients with vascular dementia (VaD) and from controls. We measured serum levels of iron, copper, ceruloplasmin, transferrin, and total antioxidant capacity (TAS), performed Apolipoprotein E (APOE) genotyping and calculated non-ceruloplasmin copper ('free' copper') levels, transferrin saturation, total iron binding capacity, and ceruloplasmin-transferrin ratio (Cp/Tf) in 93 patients with AD, 45 patients with VaD, and 48 controls. All subjects underwent biochemical, neuroimaging and cognitive evaluations. Significant differences were observed among the tested groups for the levels of copper, free copper, peroxides, and TAS and for the Cp/Tf with disparity in couple comparison. On this basis we created the M-score as linear combination of biometal variables and APOE genotype. Besides its ability to discriminate AD patients vs. controls (ROC AUC=90%), M-score was able to distinguish AD vs. VaD (ROC AUC=79%). Moreover, we calculated the sensitivity and the specificity for M-score and for the other significant variables: M-score reached the highest sensitivity without a relevant loss in terms of specificity. When we compared M-score with APOE genotype and Medial Temporal Atrophy score, it resulted statistically better than these diagnostic markers. In conclusion, we confirm the link between biometals and AD and suggest its potential as diagnostic tool. Further studies may elucidate its potential role as reliable diagnostic test.
authors.affiliation: Department of Neuroscience, AFaR - Ospedale Fatebenefratelli, 00186, Rome, Italy. rosanna.squitti@afar.it
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pasqualetti
authors.forename: Renato
authors.initials: R
authors.lastname: Polimanti
authors.forename: Carlo
authors.initials: C
authors.lastname: Salustri
authors.forename: Filomena
authors.initials: F
authors.lastname: Moffa
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cassetta
authors.forename: Domenico
authors.initials: D
authors.lastname: Lupoi
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Ventriglia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cortesi
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Siotto
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vernieri
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000235:genetics; D000704:Analysis of Variance; D000975:Antioxidants / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000097:blood; D015140:Dementia, Vascular / Q000097:blood* / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008670:Metals / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve; D014168:Transferrin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D053327:Apolipoprotein E4; D008670:Metals; D014168:Transferrin; D003300:Copper; D007501:Iron; D002570:Ceruloplasmin