Taxonomy of Neurodegenerative Diseases : Observational Study in Alzheimer's Disease and Parkinson's Disease
- Conditions
- Parkinson's DiseaseAlzheimer's Disease
- Interventions
- Other: Clinical, biological and imaging assessment
- Registration Number
- NCT05040048
- Lead Sponsor
- Institut National de la Santé Et de la Recherche Médicale, France
- Brief Summary
The AETIONOMY project will generate a refined taxonomy and testable mechanisms underlying the derived stratification of patients.
- Detailed Description
The main objective of the AETIONOMY clinical study is to test in real clinical samples the validity of the hypothesized underlying pathogenic mechanisms of AD and PD.
Although not fully understood, the pathophysiology of neurodegenerative diseases results from the complex interplay between several biological pathways such as neuronal excitotoxicity, oxidative stress, protein miss-folding and aggregation, neuroinflammation, apoptosis etc. It is thus likely that the maps generated by the AETIONOMY project will comprise several distinct biological hypotheses and subgroups of patients defined by 1 or more of these hypotheses. The Consortium has insufficient resources to validate all these hypotheses. Although it is anticipated that the AETIONOMY Project will provide novelty in the investigators' understanding of neurodegenerative diseases, it is expected that previously known biological pathways will come out from the data mining approach, e.g. mitochondrial pathway for PD or beta-amyloid aggregation for AD. AETIONOMY project will take advantage of these previously known pathways that will be considered as internal controls. One or two novel pathogenic pathways will be tested in parallel. Overall, this strategy will allow validating two hypotheses for each neurodegenerative disease (AD and PD). As it cannot be predicted what hypotheses will precisely rise from the data mining, the approach must be adaptative. However, it is possible to anticipate which population, clinical data, brain imaging procedure, and which biological samples will have to be applied for their validation. The AETIONOMY clinical study thus aims at assembling a standardized clinical, brain imaging, and biological collection from AD patients, PD patients and healthy controls to validate the model proposed by the AETIONOMY project. The Consortium will identify potential pathogenic pathways (established and novel) involved in AD and PD and will deliver surrogate markers which serve as readouts of the involved pathways. The model will be considered validated if the selected makers allow subject stratification in the AETIONOMY clinical study according to what has been postulated in the model. Additional correlation between biomarker expression and brain imaging will be performed when available. A transversal cohort will be recruited from 4 sites in Europe (France, Germany, Spain, and Sweden), including AD and PD patients, individuals at risk of AD and PD, and healthy controls.
Approximately 655 subjects will be recruited. Subjects will have a single study visit with clinical assessments, biological sampling, brain imaging (AD group only). Standardized procedures will be used for biological sampling as well as for brain image acquisition.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 220
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Parkinson's disease Group Clinical, biological and imaging assessment Blood, cerebrospinal fluid (CSF) and skin biopsy samples. Neuropsychological assessment. Motor and non motor assessments for Parkinson's disease group only. Alzheimer's disease Group Clinical, biological and imaging assessment Blood, cerebrospinal fluid (CSF) and skin biopsy samples. Neuropsychological assessment. Brain MRI for Alzheimer's disease group only.
- Primary Outcome Measures
Name Time Method Performance of the biomarker in discriminating between the taxonomy of interest and the remainder of the AD/PD subjects 27 months assessments of the effectiveness of a biomarker in assigning a taxonomy will be made using subjects with the taxonomy membership of interest and the Healthy Controls. biomarkers), surrogate of a causative mechanism for PD or AD (2 biomarkers for each disease).
AETIONOMY is built to validate the mechanism-based stratification of patients by testing in real clinical samples the hypotheses underlying pathogenic mechanisms identified by the consortium. It is expected to assess a large panel of biomarkers exploring biocollections (blood, DNA, CSF, skin biopsies) and imaging, associated with clinical assessment: (Pathway-Material for assessment (planned biomarker)) Astroglial inflammation-CSF(YKL40) Neuroinflammation-CSF and/or blood(MRP8, MRP14) Cross-talk mitochondria/neuroinflammation-CSF(TFAM, HSD10) Epigenetics-DNA(SNCA methylation) Insulin pathway-CSF and/or blood(IRS) Stress-induced comorbidity-DNA(CRH, CRHR1, MAPT) Uptake of aggregate proteins-material TBD(Syndecan)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (4)
Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Rossello 149- 153
🇪🇸Barcelona, Spain
CIC Neurosciences - ICM - Hôpital Pitié-Salpêtrière, 47-83 Bd de l'Hôpital
🇫🇷Paris, France
Universitaetsklinikum Bonn (UKB), Sigmund-Freud 25 Strasse
🇩🇪Bonn, Germany
Karolinska Institutet (KI), Karolinska University Hospital S3:01
🇸🇪Stockholm, Sweden