title: High avidity HSV-1 antibodies correlate with absence of amnestic Mild Cognitive Impairment conversion to Alzheimer's disease.
abstract: Amnestic Mild Cognitive Impairment (aMCI) is an alteration in cognitive abilities that can progress to Alzheimer's disease (AD), a condition in which herpes simplex type 1 (HSV-1) infection might play a pathogenetic role. Prognostic indexes capable of predicting aMCI conversion to AD are only partially understood. The objective of the present work is to verify whether HSV-1 immune responses is involved in conversion of aMCI to AD and correlate with grey matter brain morphometry. Two homogeneous groups of individuals who did or did not convert to AD over a 24-months period were selected after retrospective analysis of a cohort of patients with a diagnosis of aMCI. The selection of subjects was based on: a) clinical follow-up; b) neurocognitive evaluation at baseline and after 24months; c) availability of serum and DNA samples at baseline. 36 aMCI individuals, 21 of whom did (aMCI-converters) and 15 of whom did not (aMCI-non-converters) convert to AD, were included in the study. HSV-1 antibody (Ab) titers, avidity index and APOE genotyping were performed in all the enrolled individuals at baseline. Brain magnetic resonance imaging (MRI) by 1.5T scanner results at baseline were available as well in most (29/36) of these individuals. HSV-1-specific Ab titers were increased at baseline in aMCI-non-converters, and the avidity of these Ab was significantly higher in aMCI-non-converter compared to aMCI-converter (p=0.0018). Receiver operating characteristics analysis showed that HSV-1 avidity had a predictive value in distinguishing between aMCI-non-converters and aMCI-converters (p<0.0001). Notably, a positive correlation was detected as well between HSV-1 antibody titers and MRI-evaluated cortical volumes in the left hippocampus and amigdala (pcorr<0.05). In conclusion, stronger HSV-1-specific humoral responses associate with protection against AD conversion and better-preserved cortical volumes. These results reinforce the hypothesis for a role for HSV-1 in the pathogenesis of AD.
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy. Electronic address: sagostini@dongnocchi.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Agostini
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mancuso
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baglio
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Cabinio
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Hernis
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy.
authors.forename: Andrea Saul
authors.initials: AS
authors.lastname: Costa
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Calabrese
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy; Department of Physiopathology and Transplantation, University of Milano, via Fratelli Cervi 93, 20090 Milano, Italy.
authors.forename: Raffaello
authors.initials: R
authors.lastname: Nemni
authors.affiliation: Don C. Gnocchi Foundation IRCCS - ONLUS, Piazza Morandi 3, 20121 Milano, Italy; Department of Physiopathology and Transplantation, University of Milano, via Fratelli Cervi 93, 20090 Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D000647:Amnesia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000915:Antibody Affinity; D001921:Brain / Q000473:pathology / Q000821:virology; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
keywords: Avidity; Conversion to AD; HSV-1; MRI; Mild Cognitive Impairment