P75NTR, Diagnostic Biomarker for Alzheimer's Disease: Quantification Study in Cerebrospinal Fluid

Study Overview
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Brief Summary
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This research will be achieved by the assessment of p75NTR-ECD expression (total and linked to different species of Aβ (Aβ1-40 and Aβ-1-42)) within the cerebrospinal fluid (CSF) of patients with AD dementia, mild cognitive impairment (MCI) due to AD, frontotemporal dementia and non-neurodegenerative dementia.

Detailed Description
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Alzheimer's disease (AD) is a dementia which is clinically characterized by cognitive impairments with early memory loss and neuropathologically by two main lesions, amyloid deposits and tau protein accumulation. Presently, early diagnosis of AD relies on clinical symptoms, imaging techniques with recently introduced radio-tracers and analysis of cerebrospinal fluid biomarkers. All these tools are efficient when patients are already symptomatic and it is presently known that the lesions that might be reversible appear early in the time life of patients, several decades before the onset of clinical signs. To find a biomarker which would be detected early and tested in peripheral fluids is our challenge. According to updated physiopathology of the disease and referring to previous work on sphingolipid pathway in AD, precedent study focused attention on an original protein, p75NTR and particularly its extracellular domain (ECD). This protein is involved in the physiopathology of AD in several ways (apoptosis, survival). P75NTR-ECD interacts with Aβ, increases its solubility and accelerates its clearance. The hypothesis of the present study is that p75NTR-ECD could be expressed differentially according to the category and stage of dementia. More precisely, this new biomarker could help for the diagnosis of AD and could also be used as an early marker of AD when tested in peripheral fluid.

Official Title
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P75NTR, Diagnostic Biomarker for Alzheimer's Disease: Quantification Study in Cerebrospinal Fluid

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: cerebrospinal fluid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with AD patients with MCI due to AD, patients with frontotemporal dementia patients with non-neurodegenerative dementia, according to DSM-V and updated National Institute on Aging (NIA) recommendations Exclusion Criteria: patients with Parkinson disease or Lewy body dementia

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cerebrospinal fluid|Biological analysis on cerebrospinal fluid|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of p75NTR-ECD total | Concentration of p75NTR-ECD total in CSF patients | Inclusion in the present study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of p75NTR-ECD bound to Aβ1-40 and Aβ1-42 | detection in CSF from patients | Inclusion in the present study | 
| expression of p75NTR-ECD between patient groups | Differential expression of p75NTR-ECD between patient groups. Diagnostic and prognostic potential of p75NTR-ECD quantification. | inclusion in the present study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer disease, Alzheimer's disease, biomarkers, p75NTR-ECD