Alzheimer Disease
Conditions
Keywords
Enteric nervous system, Alzheimer disease, biomarker, colonic biopsies, neurodegenerative disease
Brief summary
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
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.
Interventions
OTHERbiopsies of colon
Removal of additional biopsies of colon during the course of a colonoscopy planned for usual medical follow-up of patient
Sponsors
Nantes University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | colonoscopy performed within 3 months after inclusion in the study | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | within 3 months after inclusion | 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 |
| Differences in neuronal loss in enteric submucosal tissue between patients with Alzheimer's disease, patients with Parkinson's disease and patients without neurodegenerative disease | within 3 months after inclusion | 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 |
| 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. | within 3 months after inclusion | 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 |
Contacts
PRINCIPAL_INVESTIGATORPascal DERKINDEREN, Pr
Nantes University Hospital
Outcome results
None listed