The French Series of Autosomal Dominant Early Onset Alzheimer's Disease Cases: Mutation Spectrum and Cerebrospinal Fluid Biomarkers

Article type: Research Article

Authors: Wallon, David^{a; b} | Rousseau, Stéphane^{a; b} | Rovelet-Lecrux, Anne^{a; b} | Quillard-Muraine, Muriel^c | Guyant-Maréchal, Lucie^b | Martinaud, Olivier^b | Pariente, Jérémie^d | Puel, Michèle^d | Rollin-Sillaire, Adeline^{b; e} | Pasquier, Florence^{b; e} | Le Ber, Isabelle^{b; f} | Sarazin, Marie^{b; f} | Croisile, Bernard^g | Boutoleau-Bretonnière, Claire^h | Thomas-Antérion, Catherineⁱ | Paquet, Claire^j | Moreaud, Olivier^k | Gabelle, Audrey^l | Sellal, François^m | Sauvée, Mathildeⁿ | Laquerrière, Annie^o | Duyckaerts, Charles^p | Delisle, Marie-Bernadette^q | Streichenberger, Nathalie^r | Lannes, Béatrice^s | Frebourg, Thierry^a | Hannequin, Didier^{a; b; 1} | Campion, Dominique^{a; b; 1; *} | The collaborators of the GMAJ project

Affiliations: [a] Inserm U1079, CHU et Faculté de Médecine-Pharmacie, Rouen, France | [b] CNR-MAJ, Rouen University Hospital, Lille University Hospital and Paris Salpêtrière University Hospital, Paris, France | [c] Biochemistry Laboratory, Rouen University Hospital, Rouen, France | [d] Department of Neurology, CMRR and INSERM U825, Purpan University Hospital, Toulouse, France | [e] Université Lille Nord de France, Deparment of Neurology, CHU, EA1046, Lille Nord, France | [f] CRCICM, IM2A, UMR-S975 AP-HP, University Hospital Pitié-Salpêtrière, Paris, France | [g] Department of Neuropsychology, CMRR, University Hospital, Groupe Hospitalier Est, Bron, France | [h] Department of Neurology, CMRR, Nantes University Hospital, Nantes, France | [i] Department of Neurology, CMRR, University Hospital Nord, Saint Etienne, France | [j] CMRR Nord, Lariboisière University Hospital and INSERM U839, University Paris VII, France | [k] CMRR, Grenoble University Hospital, Grenoble, France | [l] CMRR, Gui de Chauliac Hospital, Montpellier University Hospital, Montpellier, France | [m] Department of Neurology, CMRR Hôpitaux Civils de Colmar, Colmar, France | [n] Department of Neurology, CMRR, Nancy University Hospital, Nancy, France | [o] Neuropathology Laboratory, Rouen University Hospital, Rouen, France | [p] Escourolle Neuropathology Laboratory, CRCICM AP-HP, University Hospital Pitié-Salpêtrière, Paris, France | [q] Neuropathology Laboratory, Rangueil University Hospital, Toulouse, France | [r] Neuropathology Laboratory and INSERM U1028, CNRS UMR 5292, University Lyon, Lyon, France | [s] Departement of Pathology, Hautpierre Hospital, Strasbourg, France

Correspondence: [*] Correspondence to: Dr. Dominique Campion, Inserm U1079, Faculté de Médecine, 22 boulevard Gambetta, 76183 Rouen, France. Tel.: +33 235148280; Fax: +33 235148237; E-mail: [email protected].

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

Abstract: We describe 56 novel autosomal dominant early-onset Alzheimer disease (ADEOAD) families with PSEN1, PSEN2, and AβPP mutations or duplications, raising the total of families with mutations on known genes to 111 (74 PSEN1, 8 PSEN2, 16 AβPP, and 13 AβPP duplications) in the French series. In 33 additional families (23% of the series), the genetic determinism remained uncharacterized after this screening. Cerebrospinal fluid (CSF) biomarker levels were obtained for patients of 58 families (42 with known mutations and 16 without genetic characterization). CSF biomarkers profile was consistent with an AD diagnosis in 90% of families carrying mutations on known genes. In families without mutation, CSF biomarkers were consistent with AD diagnosis in 14/16 cases. Overall, these results support further genetic heterogeneity in the determinism of ADEOAD and suggest that other major genes remain to be characterized.

Keywords: Alzheimer's disease, AβPP, CSF biomarkers, early-onset, genetics, PSEN1, PSEN2

DOI: 10.3233/JAD-2012-120172

Journal: Journal of Alzheimer's Disease, vol. 30, no. 4, pp. 847-856, 2012