Definite Behavioral Variant of Frontotemporal Dementia with C9ORF72 Expansions Despite Positive Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Article type: Short Communication

Authors: Wallon, David^{a; b; 1} | Rovelet-Lecrux, Anne^{a; b; 1} | Deramecourt, Vincent^{b; c} | Pariente, Jeremie^d | Auriacombe, Sophie^e | Le Ber, Isabelle^{b; f} | Schraen, Suzanna^g | Pasquier, Florence^{b; c} | Campion, Dominique^{a; b} | Hannequin, Didier^{a; b; *}

Affiliations: [a] Inserm UMR1079 and University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France | [b] CNR-MAJ, Rouen University Hospital, Lille University Hospital and Paris Salpêtrière University Hospital, Paris, France | [c] EA1046, Memory Clinic, University Lille Nord de France, Lille University Hospital, Lille, France | [d] Department of Neurology, CMRR and INSERM U825, Purpan University Hospital, Toulouse, France | [e] CMRR Hôpital Pellegrin, Bordeaux, France | [f] CRCICM, IM2A, UMR-S975 AP-HP, University Hospital Pitié-Salpêtrière, Paris, France | [g] INSERM U837, University Lille Nord de France, Alzheimer and Tauopathies, Lille University Hospital, Lille, France

Correspondence: [*] Correspondence to: Pr. Didier Hannequin, Inserm U1079, Faculté de Médecine, 22 Boulevard Gambetta, Rouen 76183, France. Tel.: +33 235148280; Fax: +33 235148237; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Hexanucleotide expansion repeats in the C9ORF72 gene are a major cause of familial and, to a lesser extent, sporadic frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and FTLD-ALS. To examine whether C9ORF72 expansions could be involved in early-onset Alzheimer's disease (EOAD), we genotyped the hexanucleotide repeat region in a large cohort of 114 EOAD patients who all had positive AD cerebrospinal fluid (CSF) biomarkers. We found hexanucleotide expansion repeats of the C9ORF72 gene in 3 out of 114 patients (2.6%). We raise several hypotheses to explain our results and discuss the current status of AD CSF biomarkers in the dementia diagnostic algorithm.

Keywords: Alzheimer's disease, C9ORF72, cerebrospinal fluid biomarkers, dementia/diagnosis, frontotemporal lobar degeneration

DOI: 10.3233/JAD-2012-120877

Journal: Journal of Alzheimer's Disease, vol. 32, no. 1, pp. 19-22, 2012