Autosomal Dominant Cases of Alzheimer 's DiseaseGMAJNCT01622894
Genetics of Mendelian Forms of Young Onset Alzheimer Disease
A study testing Genetic-Tailored AntiThrombotic Strategy in people with Autosomal Dominant Cases of Alzheimer 's Disease, run by University Hospital, Rouen at 1 site in France.
Trial summary
Genetics of mendelian forms of young onset Alzheimer Disease (GMAJ project) Introduction : Autosomal dominant forms of Alzheimer disease (AD) are characterized by young age of onset. In France the prevalence was estimated at around 1000 cases. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Autosomal Dominant Cases of Alzheimer 's Disease
- What is being tested?
- Genetic-Tailored AntiThrombotic Strategy
- How many people
- 150 participants
- Where
- 1 siteFrance
- Study dates
- 15 Nov 2009to 15 Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- > in one family 2 cases of Alzheimer disease with age of onset under 65
Who cannot join
- other cases of young onset dementia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Genetics of Mendelian Forms of Young Onset Alzheimer Disease. Identification of Novel Genetic Causes of AD Are of Importance in Completing the Mechanisms of the Amyloid Hypothesis. This Project is Useful to Promote the Guidelines on the Genetic Diagnosis of AD in France.
Genetics of mendelian forms of young onset Alzheimer Disease (GMAJ project)
Introduction : Autosomal dominant forms of Alzheimer disease (AD) are characterized by young age of onset. In France the prevalence was estimated at around 1000 cases. The Phenotypical Expression: There is diversity in phenotypical expression, associating dementia, spastic paraplegia, early extrapyramidal syndrome, ataxia or stroke caused by severe cerebral amyloid angiopathy. Diversity in neuropathological expression is demonstrated by the presence of cotton wool plaques, Lewy bodies with Lewy neurites and severe cerebral amyloid angiopathy.
Read more
The study of mendelian forms is decisive in the physiopathological comprehension of AD and related diseases, since the alteration of those genes involved is sufficient to cause the disease. In AD, identification of these genetic causes allows the formulation of the amyloid hypothesis, which is the basis of current therapeutic developments concerning the Ab peptide. Currently three genes (APP, PSEN1, PSEN2) are identified in early onset mendelian forms and their mutations are involved in 80% of the 139 French families, studied since 1993 within the framework of U614 and the National Reference Centre for Alzheimer Disease in young subjects (CNR-MAJ).These results are arguments in favor of the GMAJ project and have two main objectives:
(i) to identify new genes in mendelian AD forms without detectable alteration on known genes.
(ii) to correlate phenotypes and genotypes within families associated with known mutations and extend the description of the phenotypical spectrum.
Population: Families eligible for this study are those with at least 2 individuals with AD criteria (clinical or neuropathological) with onset before 65 years of age. Duration of inclusion is 3 years. This multicentre study groups 23 clinical centres. The inclusion number is 50 new families per year.
Method: Extension and description of families with unknown genetic causes, inclusion of novel families with autosomal dominant AD. The successive steps of the project are the following:
(i) Thorough phenotypical characterization in order to document family history and characterize the probands and affected related subjects according to standardized protocol for clinical, neuropsychological, biological (biomarker determination in plasma and cerebrospinal fluid) and imaging data (MRI, TEMP).
(ii) Identify known genetic causes (PSEN1/2, APP) with novel autosomal dominant families.
(iii) Extend analysis of the pedigrees of families with unknown genetic causes.
(iv) Identify novel genetic causes within these families which are negative for known mutations.
This study uses 3 methods:
- pangenomic search is performed for microalterations (Copy Number Variants or CNV) by Comparative Genomic Hybridization (CGH) with high resolution (10 kb on average).
- potential targets are then validated by the study of large control populations, intrafamilial cosegregation and functional validation.
- the remaining families at the end of this stage will be characterized by means of high throughput sequencing of all exonic areas. (v) Follow up study of patients and siblings with 2 goals:
- evaluation of the disease course and consequences (individual, familial and social);
- occurrence of novel AD cases within the family. (vi) Neuropathological description with potential novel description of atypical AD cases.
Results and consequences: Identification of novel genetic causes of AD are of importance in completing the mechanisms of the amyloidergic hypothesis. This project is useful to promote the guidelines on the genetic diagnosis of AD in France.
- Being tested
- Genetic-Tailored AntiThrombotic Strategy
- Keywords
- Alzheimer genetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic-Tailored AntiThrombotic StrategyGenetic
genetic
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2012 (estimated)
- Study start15 Nov 2009
- Primary completion15 Dec 2018
- Study completion15 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Cases of Alzheimer 's DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Didier HANNEQUIN, Pr, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01622894
- Sponsor's protocol ID
- 2008/067/HP
- Acronym
- GMAJ
- Status last verified
- Apr 2026
- First submitted
- 14 Jun 2012
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nicolas G, Wallon D, Charbonnier C, Quenez O, Rousseau S, Richard AC, Rovelet-Lecrux A, Coutant S, Le Guennec K, Bacq D, Garnier JG, Olaso R, Boland A, Meyer V, Deleuze JF, Munter HM, Bourque G, Auld D, Montpetit A, Lathrop M, Guyant-Marechal L, Martinaud O, Pariente J, Rollin-Sillaire A, Pasquier F, Le Ber I, Sarazin M, Croisile B, Boutoleau-Bretonniere C, Thomas-Anterion C, Paquet C, Sauvee M, Moreaud O, Gabelle A, Sellal F, Ceccaldi M, Chamard L, Blanc F, Frebourg T, Campion D, Hannequin D. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons. Eur J Hum Genet. 2016 May;24(5):710-6. doi: 10.1038/ejhg.2015.173. Epub 2015 Aug 5.
PubMed 26242991Nicolas G, Charbonnier C, Wallon D, Quenez O, Bellenguez C, Grenier-Boley B, Rousseau S, Richard AC, Rovelet-Lecrux A, Le Guennec K, Bacq D, Garnier JG, Olaso R, Boland A, Meyer V, Deleuze JF, Amouyel P, Munter HM, Bourque G, Lathrop M, Frebourg T, Redon R, Letenneur L, Dartigues JF, Genin E, Lambert JC, Hannequin D, Campion D; CNR-MAJ collaborators. SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease. Mol Psychiatry. 2016 Jun;21(6):831-6. doi: 10.1038/mp.2015.121. Epub 2015 Aug 25.
PubMed 26303663Nicolas G, Wallon D, Goupil C, Richard AC, Pottier C, Dorval V, Sarov-Riviere M, Riant F, Herve D, Amouyel P, Guerchet M, Ndamba-Bandzouzi B, Mbelesso P, Dartigues JF, Lambert JC, Preux PM, Frebourg T, Campion D, Hannequin D, Tournier-Lasserve E, Hebert SS, Rovelet-Lecrux A. Mutation in the 3'untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy. Eur J Hum Genet. 2016 Jan;24(1):92-8. doi: 10.1038/ejhg.2015.61. Epub 2015 Apr 1.
PubMed 25828868Rovelet-Lecrux A, Charbonnier C, Wallon D, Nicolas G, Seaman MN, Pottier C, Breusegem SY, Mathur PP, Jenardhanan P, Le Guennec K, Mukadam AS, Quenez O, Coutant S, Rousseau S, Richard AC, Boland A, Deleuze JF, Frebourg T, Hannequin D, Campion D; CNR-MAJ collaborators. De novo deleterious genetic variations target a biological network centered on Abeta peptide in early-onset Alzheimer disease. Mol Psychiatry. 2015 Sep;20(9):1046-56. doi: 10.1038/mp.2015.100. Epub 2015 Jul 21.
PubMed 26194182
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetics of Mendelian Forms of Young Onset Alzheimer Disease. Identification of Novel Genetic Causes of AD Are of Importance in Completing the Mechanisms of the Amyloid Hypothesis. This Project is Useful to Promote the Guidelines on the Genetic Diagnosis of AD in France.
- ClinicalTrials.gov ID
- NCT01622894
- Acronym / sponsor ID
- GMAJ / 2008/067/HP
- Keywords
- Alzheimer genetics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 15 Nov 2009 (actual)
- Primary completion
- 15 Dec 2018 (actual)
- Study completion
- 15 Dec 2018 (actual)
- First posted
- 19 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Genetics of mendelian forms of young onset Alzheimer Disease (GMAJ project)
Introduction : Autosomal dominant forms of Alzheimer disease (AD) are characterized by young age of onset. In France the prevalence was estimated at around 1000 cases. The Phenotypical Expression: There is diversity in phenotypical expression, associating dementia, spastic paraplegia, early extrapyramidal syndrome, ataxia or stroke caused by severe cerebral amyloid angiopathy. Diversity in neuropathological expression is demonstrated by the presence of cotton wool plaques, Lewy bodies with Lewy neurites and severe cerebral amyloid angiopathy.
The study of mendelian forms is decisive in the physiopathological comprehension of AD and related diseases, since the alteration of those genes involved is sufficient to cause the disease. In AD, identification of these genetic causes allows the formulation of the amyloid hypothesis, which is the basis of current therapeutic developments concerning the Ab peptide. Currently three genes (APP, PSEN1, PSEN2) are identified in early onset mendelian forms and their mutations are involved in 80% of the 139 French families, studied since 1993 within the framework of U614 and the National Reference Centre for Alzheimer Disease in young subjects (CNR-MAJ).These results are arguments in favor of the GMAJ project and have two main objectives:
(i) to identify new genes in mendelian AD forms without detectable alteration on known genes.
(ii) to correlate phenotypes and genotypes within families associated with known mutations and extend the description of the phenotypical spectrum.
Population: Families eligible for this study are those with at least 2 individuals with AD criteria (clinical or neuropathological) with onset before 65 years of age. Duration of inclusion is 3 years. This multicentre study groups 23 clinical centres. The inclusion number is 50 new families per year.
Method: Extension and description of families with unknown genetic causes, inclusion of novel families with autosomal dominant AD. The successive steps of the project are the following:
(i) Thorough phenotypical characterization in order to document family history and characterize the probands and affected related subjects according to standardized protocol for clinical, neuropsychological, biological (biomarker determination in plasma and cerebrospinal fluid) and imaging data (MRI, TEMP).
(ii) Identify known genetic causes (PSEN1/2, APP) with novel autosomal dominant families.
(iii) Extend analysis of the pedigrees of families with unknown genetic causes.
(iv) Identify novel genetic causes within these families which are negative for known mutations.
This study uses 3 methods:
- pangenomic search is performed for microalterations (Copy Number Variants or CNV) by Comparative Genomic Hybridization (CGH) with high resolution (10 kb on average).
- potential targets are then validated by the study of large control populations, intrafamilial cosegregation and functional validation.
- the remaining families at the end of this stage will be characterized by means of high throughput sequencing of all exonic areas. (v) Follow up study of patients and siblings with 2 goals:
- evaluation of the disease course and consequences (individual, familial and social);
- occurrence of novel AD cases within the family. (vi) Neuropathological description with potential novel description of atypical AD cases.
Results and consequences: Identification of novel genetic causes of AD are of importance in completing the mechanisms of the amyloidergic hypothesis. This project is useful to promote the guidelines on the genetic diagnosis of AD in France.
Study design
- Primary purpose
- Other
- Masking
- Single blind (participant)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- > in one family 2 cases of Alzheimer disease with age of onset under 65
Key exclusion criteria (1 listed)
- other cases of young onset dementia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genetic-Tailored AntiThrombotic Strategygenetic | Genetic | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Results publication: PubMed 26242991Nicolas G, Wallon D, Charbonnier C, Quenez O, Rousseau S, Richard AC, Rovelet-Lecrux A, Coutant S, Le Guennec K, Bacq D, Garnier JG, Olaso R, Boland A, Meyer V, Deleuze JF, Munter HM, Bourque G, Auld D, Montpetit A, Lathrop M, Guyant-Marechal L, Martinaud O, Pariente J, Rollin-Sillaire A, Pasquier F, Le Ber I, Sarazin M, Croisile B, Boutoleau-Bretonniere C, Thomas-Anterion C, Paquet C, Sauvee M, Moreaud O, Gabelle A, Sellal F, Ceccaldi M, Chamard L, Blanc F, Frebourg T, Campion D, Hannequin D. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons. Eur J Hum Genet. 2016 May;24(5):710-6. doi: 10.1038/ejhg.2015.173. Epub 2015 Aug 5.
- Results publication: PubMed 26303663Nicolas G, Charbonnier C, Wallon D, Quenez O, Bellenguez C, Grenier-Boley B, Rousseau S, Richard AC, Rovelet-Lecrux A, Le Guennec K, Bacq D, Garnier JG, Olaso R, Boland A, Meyer V, Deleuze JF, Amouyel P, Munter HM, Bourque G, Lathrop M, Frebourg T, Redon R, Letenneur L, Dartigues JF, Genin E, Lambert JC, Hannequin D, Campion D; CNR-MAJ collaborators. SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease. Mol Psychiatry. 2016 Jun;21(6):831-6. doi: 10.1038/mp.2015.121. Epub 2015 Aug 25.
- Results publication: PubMed 25828868Nicolas G, Wallon D, Goupil C, Richard AC, Pottier C, Dorval V, Sarov-Riviere M, Riant F, Herve D, Amouyel P, Guerchet M, Ndamba-Bandzouzi B, Mbelesso P, Dartigues JF, Lambert JC, Preux PM, Frebourg T, Campion D, Hannequin D, Tournier-Lasserve E, Hebert SS, Rovelet-Lecrux A. Mutation in the 3'untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy. Eur J Hum Genet. 2016 Jan;24(1):92-8. doi: 10.1038/ejhg.2015.61. Epub 2015 Apr 1.
- Results publication: PubMed 26194182Rovelet-Lecrux A, Charbonnier C, Wallon D, Nicolas G, Seaman MN, Pottier C, Breusegem SY, Mathur PP, Jenardhanan P, Le Guennec K, Mukadam AS, Quenez O, Coutant S, Rousseau S, Richard AC, Boland A, Deleuze JF, Frebourg T, Hannequin D, Campion D; CNR-MAJ collaborators. De novo deleterious genetic variations target a biological network centered on Abeta peptide in early-onset Alzheimer disease. Mol Psychiatry. 2015 Sep;20(9):1046-56. doi: 10.1038/mp.2015.100. Epub 2015 Jul 21.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Didier HANNEQUIN, Pr principal investigator
University Hospital, Rouen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Genetic-Tailored AntiThrombotic Strategy in people with Autosomal Dominant Cases of Alzheimer 's Disease, run by University Hospital, Rouen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01622894, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.