Taxonomy of Neurodegenerative Diseases : Observational Study in Alzheimer's Disease and Parkinson's Disease
Condition: Alzheimer's Disease; Parkinson's Disease
MeSH terms: Parkinson Disease; Alzheimer Disease; Neurodegenerative Diseases
Study type: Observational

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.
    

Intervention name(s): Clinical, biological and imaging assessment
Intervention type(s): Other
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        PD GROUP (n=325):

          -  240 idiopathic PD patients

          -  40 PD patients with mutations of the gene of Parkin (n =10), LRRK2 (n=10) and GBA
             (n=20)

          -  45 subjects at risk of PD:

               -  first degree relative of a PD index case with mutation (LRRK2, n=10)

               -  first degree relative of a PD index case with risk factor (GBA, n=10)

               -  subjects with idiopathic RBD (n=25)

        AD GROUP (n=150):

          -  90 prodromal AD patients

          -  60 preclinical AD patients

        HEALTHY CONTROLS (n=180):

          -  90 healthy controls matched for age and sex for PD group's subject

          -  90 healthy controls matched for age and sex for AD group's subject
      
Biospecimen description: 
      blood and CSF samples
    
Keywords: Alzheimer; Parkinson; Data mining; Biomarkers; Stratification