Exploration of the Enteric Nervous System in Alzheimer Disease

Study Overview
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Brief Summary
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The close homology between the central and enteric nervous system suggests that a disease process affecting the central nervous system could also involve its enteric counterpart. This has already been demonstrated for patients with Parkinson's disease but needs to be proven for Alzheimer's disease. Studies on enteric nervous system during Alzheimer's disease are indeed in low number and don't have led to definite conclusion. The investigators thus propose to realize a complete analysis of the enteric nervous systems in Alzheimer's disease by studying the presence of tau' protein, of beta-amyloid peptide,... not only by immunohistochemical but also by a biochemical approach. This study will be realized from colonic samples.

Detailed Description
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The close homology between the central and enteric nervous system suggests that a disease process affecting the central nervous system could also involve its enteric counterpart. The investigators have recently shown in that the enteric neurons can be readily analyzed using routine colonic biopsies. The investigators propose that the enteric nervous system could represent a unique window to assess the neuropathology in living patients with a neurodegenerative disorder. The investigators have already used this approach to show that Parkinson's disease pathology was recapitulated in a single colonic biopsy. By contrast to Parkinson's disease, the detection of Alzheimer's disease pathology in the enteric neurons has so far failed. This may be due to the low number of human tissue samples in addition to the low sensitivity of the immunohistochemical methods that were used. The aim of the current research project will be therefore to reevaluate Alzheimer's disease pathology in a large number of human colonic samples using both a morphological and biochemical approach. The Hypothesis is that the enteric nervous system could represent a unique window to assess the neuropathology in living patients with Alzheimer's disease. This might open the way to the development of novel Alzheimer's disease biomarkers that will directly assess the neuropathological process.

Official Title
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Exploration of the Enteric Nervous System in Alzheimer Disease : a Monocentric Pilot Study

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Other: biopsies of colon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For the 3 groups of patients : colonoscopy planned by a gastroenterologist in the context ot the usual medical follow-up of the patient For patients with Alzheimer's disease : Patient with early to moderate Alzheimer disease (continuum of patients with mild cognitive impairment due to Alzheimer's disease and patients diagnosed with probable Alzheimer's disease) according to the National Institute of Aging-Alzheimer's Association (NIA AA) criteria Mini-Mental State Examination (MMSE) score ≥18; Has one informant or care partner; No parkinsonian syndrome No sign of lewy Body dementia For patients with Parkinson's disease: patients with Parkinson Disease according to the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria No dementia sign or cognitive deficit associated to Alzheimer's disease For patients without neurodegenerative disease: No history or current neurological/degenerative condition (e.g, lewy body dementia, Parkinson's disease, Parkinsonian syndrome, Alzheimer's disease,…) No memory complaint with a Mac Nair score ≤15 MMSE score ≥28 ; Patient at risk of colic cancer with a colonoscopy scheduled Exclusion Criteria: For the 3 groups of patients : : History of colonic disorder ((e.g inflammatory condition, adenocarcinoma) contra-indications to colonoscopy For patients with Alzheimer's disease and for patients with Parkinson's disease: - Any neurological/neurodegenerative condition different from the group to which it belongs (e.g other than Alzheimer's disease for Alzheimer's disease group or other than Parkinson's disease for Parkinson's disease group….) For patients without neurodegenerative disease: Any neurological/neurodegenerative condition (e.g lewy body dementia, Parkinsonian syndrome, Parkinson's disease, Alzheimer's disease..).. functional colopathy

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3 types of patients will be included: 10 patients with Alzheimer's disease and as controls: 10 patients with Parkinson's disease 10 patients without neurodegenerative disease. During the course of the colonoscopy that these 30 patients should have in the context of their medical usual care, additionnal biopsies of colon will be removed to perform in vitro analysis for this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patients with Alzheimer's disease<br>During the course of the colonoscopy that the patients should have in the context of their usual medical care, additional biopsies of colon will be removed to perform in vitro analysis for this study. | Other: biopsies of colon<br>* Removal of additional biopsies of colon during the course of a colonoscopy planned for usual medical follow-up of patient<br>|
| Other: Patients with Parkinson's disease<br>During the course of the colonoscopy that the patients should have in the context of their usual medical care, additional biopsies of colon will be removed to perform in vitro analysis for this study. | Other: biopsies of colon<br>* Removal of additional biopsies of colon during the course of a colonoscopy planned for usual medical follow-up of patient<br>|
| Other: Patients without neurodegenerative disease<br>During the course of the colonoscopy that the patients should have in the context of their usual medical care, additional biopsies of colon will be removed to perform in vitro analysis for this study. | Other: biopsies of colon<br>* Removal of additional biopsies of colon during the course of a colonoscopy planned for usual medical follow-up of patient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in extracellular deposits of beta-amyloid peptide in the enteric nervous system between patients with Alzheimer's disease, patients with Parkinson's disease and patients without neurodegenerative disease. | In vitro analysis of the presence of beta-amyloid peptide in biopsies of colon from patients with Alzheimer's disease ans as controls from patients with Parkinson's disease and from patients without neurodegenerative disease | colonoscopy performed within 3 months after inclusion in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in tau protein in the enteric nervous system between patients with Alzheimer's disease, patients with Parkinson's disease and patients without neurodegenerative disease. | In vitro analysis of the presence of tau protein in biopsies of colon from patients with Alzheimer's disease ans as controls from patients with Parkinson's disease and from patients without neurodegenerative disease | within 3 months after inclusion | 
| Differences in neuronal loss in enteric submucosal tissue between patients with Alzheimer's disease, patients with Parkinson's disease and patients without neurodegenerative disease | In vitro analysis of the presence of neuronal loss in biopsies of colon from patients with Alzheimer's disease ans as controls from patients with Parkinson's disease and from patients without neurodegenerative disease | within 3 months after inclusion | 
| Differences in neuronal Glia cells in the enteric nervous system between patients with Alzheimer's disease, patients with Parkinson's disease and patients without neurodegenerative disease. | In vitro analysis of the presence neuronal glia cells in biopsies of colon from patients with Alzheimer's disease ans as controls from patients with Parkinson's disease and from patients without neurodegenerative disease | within 3 months after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enteric nervous system, Alzheimer disease, biomarker, colonic biopsies, neurodegenerative disease