The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers.

David Wallon , Stéphane Rousseau (1) , Anne Rovelet-Lecrux (2) , Muriel Quillard-Muraine , Lucie Guyant-Maréchal (3) , Olivier Martinaud (4) , Jérémie Pariente (5) , Michèle Puel (5, 6) , Adeline Rollin-Sillaire , Florence Pasquier (7) , Isabelle Le Ber (8) , Marie Sarazin , Bernard Croisile (9) , Claire Boutoleau-Bretonnière (10) , Catherine Thomas-Antérion (11) , Claire Paquet (12) , Olivier Moreaud (13, 14) , Audrey Gabelle (15, 16, 17) , François Sellal (18) , Mathilde Sauvée , Annie Laquerrière (19) , Charles Duyckaerts (20) , Marie-Bernadette Delisle (21) , Nathalie Streichenberger (22) , Béatrice Lannes , Thierry Frebourg (23) , Didier Hannequin (23) , Dominique Campion (24) , Non Renseigné

1 Thales Communications [Colombes]
2 Service de neurologie [Rouen]
3 Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques
4 CHU Rouen
5 ICHN - Imagerie cérébrale et handicaps neurologiques
6 Neurologie générale et maladies inflammatoires du système nerveux [Toulouse]
7 Département de neurologie [Lille]
8 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
9 Département de Neurologie
10 Service de neurologie [Nantes]
11 CMRR - Centre de Mémoire de Ressource et Recherche
12 Institut du Fer à Moulin
13 LPNC - Laboratoire de Psychologie et NeuroCognition
14 Unité de Neuropsychologie
15 IGH - Institut de génétique humaine
16 IRB - Institut de recherche en biothérapie
17 Cellules souches normales et cancéreuses
18 Service de neurologie
19 Service d'Anatomie et Cytologie Pathologique [CHU Rouen]
20 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
21 CRCT - Centre de Recherches en Cancérologie de Toulouse
22 Services de Neurochimie et de Pathologie
23 GMFC - Génétique du cancer et des maladies neuropsychiatriques
24 Service de neurologie [Rouen]

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.

Domaines: Neurosciences [q-bio.NC]

David Wallon, Stéphane Rousseau, Anne Rovelet-Lecrux, Muriel Quillard-Muraine, Lucie Guyant-Maréchal, et al.. The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers.. Journal of Alzheimer's Disease, 2012, 30 (4), pp.847-56. ⟨10.3233/JAD-2012-120172⟩. ⟨hal-00965220⟩