title: Frontotemporal dementia and language networks: cortical thickness reduction is driven by dyslexia susceptibility genes.
abstract: Variations within genes associated with dyslexia result in a language network vulnerability, and in patients with Frontotemporal Dementia (FTD), language disturbances represent a disease core feature. Here we explored whether variations within three related-dyslexia genes, namely KIAA0319, DCDC2, and CNTNAP, might affect cortical thickness measures in FTD patients. 112 FTD patients underwent clinical and neuropsychological examination, genetic analyses and brain Magnetic Resonance Imaging (MRI). KIAA0319 rs17243157 G/A, DCDC2 rs793842 A/G and CNTNAP2 rs17236239 A/G genetic variations were assessed. Cortical thickness was analysed by Freesurfer. Patients carrying KIAA0319 A*(AG or AA) carriers showed greater cortical thickness atrophy in the left fusiform and inferior temporal gyri, compared to KIAA0319 GG (p ≤ 0.001). Patients carrying CNTNAP2 G*(GA or GG) showed reduced cortical thickness in the left insula thenCNTNAP2 AA carriers (p≤0.001). When patients with both at-risk polymorphisms were considered (KIAA0319 A* and CNTNAP2 G*), greater and addictive cortical thickness atrophy of the left insula and the inferior temporal gyrus was demonstrated (p ≤ 0.001). No significant effect of DCDC2 was found. In FTD, variations of KIAA0319 and CNTNAP2 genes were related to cortical thickness abnormalities in those brain areas involved in language abilities. These findings shed light on genetic predisposition in defining phenotypic variability in FTD.
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Paternicó
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Manes
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Premi
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Cosseddu
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gazzina
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Alberici
authors.affiliation: The III Laboratory, Biotechnology, Spedali Civili Hospital, Brescia, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bonomi
authors.affiliation: Neurology Unit, Valle Camonica Hospital, Brescia, Italy.
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Cotelli
authors.affiliation: IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cotelli
authors.affiliation: Neurology Unit, Valle Camonica Hospital, Brescia, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Turla
authors.affiliation: Casa di Cura S. Francesco, Bergamo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Micheli
authors.affiliation: The Neuroradiology Unit, University of Brescia, Brescia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gasparotti
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Centre of Brain Aging, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
mesh_terms: D000368:Aged; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D004410:Dyslexia / Q000235:genetics / Q000473:pathology*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics / Q000473:pathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007806:Language Disorders / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: C403049:CNTNAP2 protein, human; C510451:DCDC2 protein, human; C500377:KIAA0319 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins