Exploration of the Enteric Nervous System in Alzheimer Disease : a Monocentric Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Patients with Alzheimer's disease
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.
干预措施: biopsies of colon (Other)
Patients with Parkinson's disease
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.
干预措施: biopsies of colon (Other)
Patients without neurodegenerative disease
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.
干预措施: biopsies of colon (Other)
结局指标
主要结局
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.
时间窗: 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
次要结局
- 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)
- 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)
- 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)