Clinical and Genetic Study of Neurodegenerative Disorders With Cognitive Impairment

Patients with different types of dementia will be recruited and evaluated in national hospital departments for their usual neurological follow-ups. A blood sample will be proposed in the field of this research project, and the biological material will be stored at the DNA and Cell Bank of Institut de Fédératif Recherche (IFR) of Neurosciences (Pitié-Salpêtrière Hospital, Paris). The clinical research network is already set up for Alzheimer's disease and frontotemporal dementias, which permits an evaluation according to a clinical standardized protocol.

Among these disorders, a monogenic sub-group has been identified. In Alzheimer's disease, it is associated with the APP, PSEN1 and PSEN2 genes, which account only for 75% of the familial forms with early onset. In frontotemporal dementias, the tau gene mutations account only for 10% of the cases with an autosomal dominant inheritance. The identification of familial forms with a genetic inquiry in the relatives is essential for a greater knowledge of the molecular bases of forms not caused by the known genes, using linkage approaches and candidate gene analysis. The familial forms are also useful for identifying the modifier genes.

In the multifactorial forms, the aim is to assemble a wide cohort of patients and controls matched for localizing and identifying susceptibility genetic factors. The strategies will use a candidate gene approach, and in the near future, studies of single nucleotide polymorphisms (SNPs) spread out in the whole genome. Meanwhile, similar approaches, particularly with candidate genes, could be used for identifying predictive factors of tolerance and response to the treatment.

Finally, correlations will be performed with seric markers according to each kind of dementia.

Specialized clinical teams in diagnosis and follow-up in dementias are assembled for this project, and in the study of neurological disorders of genetic origin.

Study Overview

• Status: Unknown
• Conditions: Dementia; Alzheimer's Disease; Neurodegenerative Disorders
• Intervention / Treatment: Other: Blood sampling, skin biopsy

• Study Type: Observational
• Enrollment (Anticipated): 4000

Contacts and Locations

• Study Contact: Name: Alexis Brice, MD; Phone Number: 0033142162182; Email: brice@ccr.jussieu.fr

Study Locations

• France
  • Caen, France, 14000
    • Recruiting
    • CHU de la cote de Nacre
    • Contact: Gilles Defer, MD, PhD
    • Principal Investigator: Gilles Defer, MD, PhD
    • Sub-Investigator: Isabelle Le Ber, MD
  • Marseille, France, 13009
    • Recruiting
    • Hôpital Sainte-Marguerite
    • Contact: Bernard-François Michel, MD; Phone Number: 0033491744949; Email: bmichel@ap-hm.fr
    • Principal Investigator: Bernard-François Michel, MD
  • Nantes, France, 44000
    • Recruiting
    • Hopital Guillaume Et Rene Laennec
    • Contact: Martine Vercelletto, MD; Phone Number: 0033240165422; Email: mvercelletto@chu-nantes.fr
    • Principal Investigator: Martine Vercelletto, MD
  • Nice, France, 06000
    • Recruiting
    • Hopital de l'Archet
    • Contact: Claude Desnuelle, MD, PhD; Phone Number: 0033492035505; Email: desnuelle.c@chu-nice.fr
    • Principal Investigator: Claude Desnuelle, MD, PhD
    • Sub-Investigator: Marie-Hélène Soriani, MD
  • Paris, France, 75013
    • Recruiting
    • Pitie-Salpêtrière Hospital
    • Contact: Alexis Brice, MD; Phone Number: 0033142162182; Email: brice@ccr.jussieu.fr
    • Sub-Investigator: Isabelle Le Ber, MD
  • Paris, France, 75013
    • Recruiting
    • Pitié-Salpêtrière Hospital - Centre du Langage et de Neuropsychologie
    • Contact: Bruno Dubois, MD; Phone Number: 0033142161777; Email: b.dubois@psl.ap-hop-paris.fr
    • Principal Investigator: Bruno Dubois, MD
  • Paris, France, 75013
    • Recruiting
    • Pitié-Salpêtrière Hospital - Fédération de Neurologie
    • Contact: Vincent Meininger, MD, PhD; Email: vincent.meininger@psl.aphp.fr
    • Principal Investigator: Vincent Meininger, MD, PhD
    • Sub-Investigator: Lucette Lacomblez, MD
    • Sub-Investigator: François Salachas, MD
  • Rennes, France, 35000
    • Recruiting
    • Hôpital Pontchaillou
    • Contact: Serge Belliard, MD; Phone Number: 0033299284293; Email: belliard.s@voila.fr
    • Principal Investigator: Serge Belliard, MD
    • Sub-Investigator: Véronique Golfier, MD
  • Rouen, France, 76000
    • Recruiting
    • Hopital Charles Nicolle
    • Contact: Didier Hannequin, MD, PhD; Phone Number: 0033232888170; Email: Didier.hannequin@chu-rouen.fr
    • Principal Investigator: Didier Hannequin, MD, PhD
  • Saint-Brieuc, France, 22000
    • Recruiting
    • Centre Hospitalier
    • Contact: Véronique Golfier, MD; Phone Number: 0033296017454; Email: veronique.golfier@ch-stbrieuc.fr
    • Principal Investigator: Véronique Golfier, MD
  • Saint-Etienne, France, 42000
    • Recruiting
    • Hopital Bellevue
    • Contact: Catherine Thomas-Antérion, MD; Phone Number: 0033477127805; Email: catherine.thomas@chu-st-etienne.fr
    • Principal Investigator: Catherine Thomas-Antérion, MD
  • Strasbourg, France, 67000
    • Recruiting
    • Hopital Civil
    • Contact: François Sellal, MD; Phone Number: 0033388116892; Email: Francois.Sellal@chru-strasbourg.fr
    • Principal Investigator: François SELLAL, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Patients presenting with a neurodegenerative disorder
• At risk patients

Description

Inclusion Criteria:

• Patients presenting with a neurodegenerative disorder with cognitive impairment controls (without signs of the disease), matched with sex and age with the patients
• Relatives for the familial cases

Exclusion Criteria:

• Pregnant women
• Minors
• Persons refusing to sign the informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control	Other: Blood sampling, skin biopsy; Blood sampling, skin biopsy in the field of the medical follow-up
Neurodegenerative disorders with cognitive impairment	Other: Blood sampling, skin biopsy; Blood sampling, skin biopsy in the field of the medical follow-up
At risk reactive	Other: Blood sampling, skin biopsy; Blood sampling, skin biopsy in the field of the medical follow-up

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: Aventis Pharmaceuticals

Publications and helpful links

General Publications

• Le Ber I, Guedj E, Gabelle A, Verpillat P, Volteau M, Thomas-Anterion C, Decousus M, Hannequin D, Vera P, Lacomblez L, Camuzat A, Didic M, Puel M, Lotterie JA, Golfier V, Bernard AM, Vercelletto M, Magne C, Sellal F, Namer I, Michel BF, Pasquier J, Salachas F, Bochet J; French research network on FTD/FTD-MND; Brice A, Habert MO, Dubois B. Demographic, neurological and behavioural characteristics and brain perfusion SPECT in frontal variant of frontotemporal dementia. Brain. 2006 Nov;129(Pt 11):3051-65. doi: 10.1093/brain/awl288.
• van der Zee J, Le Ber I, Maurer-Stroh S, Engelborghs S, Gijselinck I, Camuzat A, Brouwers N, Vandenberghe R, Sleegers K, Hannequin D, Dermaut B, Schymkowitz J, Campion D, Santens P, Martin JJ, Lacomblez L, De Pooter T, Peeters K, Mattheijssens M, Vercelletto M, Van den Broeck M, Cruts M, De Deyn PP, Rousseau F, Brice A, Van Broeckhoven C. Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. Hum Mutat. 2007 Apr;28(4):416. doi: 10.1002/humu.9484.
• Baba Y, Baker MC, Le Ber I, Brice A, Maeck L, Kohlhase J, Yasuda M, Stoppe G, Bugiani O, Sperfeld AD, Tsuboi Y, Uitti RJ, Farrer MJ, Ghetti B, Hutton ML, Wszolek ZK. Clinical and genetic features of families with frontotemporal dementia and parkinsonism linked to chromosome 17 with a P301S tau mutation. J Neural Transm (Vienna). 2007 Jul;114(7):947-50. doi: 10.1007/s00702-007-0632-9. Epub 2007 Feb 23.
• Le Ber I, van der Zee J, Hannequin D, Gijselinck I, Campion D, Puel M, Laquerriere A, De Pooter T, Camuzat A, Van den Broeck M, Dubois B, Sellal F, Lacomblez L, Vercelletto M, Thomas-Anterion C, Michel BF, Golfier V, Didic M, Salachas F, Duyckaerts C, Cruts M, Verpillat P, Van Broeckhoven C, Brice A; French Research Network on FTD/FTD-MND. Progranulin null mutations in both sporadic and familial frontotemporal dementia. Hum Mutat. 2007 Sep;28(9):846-55. doi: 10.1002/humu.20520.
• Guedj E, Le Ber I, Lacomblez L, Dubois B, Verpillat P, Didic M, Salachas F, Vera P, Hannequin D, Lotterie JA, Puel M, Decousus M, Thomas-Anterion C, Magne C, Vercelletto M, Bernard AM, Golfier V, Pasquier J, Michel BF, Namer I, Sellal F, Bochet J, Volteau M, Brice A, Meininger V; French Research Network on FTD/FTD-MND; Habert MO. Brain spect perfusion of frontotemporal dementia associated with motor neuron disease. Neurology. 2007 Jul 31;69(5):488-90. doi: 10.1212/01.wnl.0000266638.53185.e7. No abstract available.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Study Completion (ANTICIPATED): October 1, 2007

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 6, 2005
• First Posted (ESTIMATE): September 8, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): March 15, 2010
• Last Update Submitted That Met QC Criteria: March 12, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Dementia; Candidate genes; Phenotype-genotype correlations; Related disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Tauopathies; Cognition Disorders; Disease; Dementia; Alzheimer Disease; Cognitive Dysfunction; Neurodegenerative Diseases
• Other Study ID Numbers: 02-156; 02-346A10