Detection of fecal amyloid in subjects with early stage Alzheimer’s disease

Résumé 0

Introduction: Alzheimer’s disease (AD) is the most frequent form of dementia in the Western world and its prevalence is estimated at 4.4% in the over 65 years and more than 25% in the over 90 years. It is characterized by the deposition of beta amyloid and tau peptides in the brain. To help with clinical diagnosis (neuropsychological evaluation, functional and psychiatric endpoints), CSF biomarkers, by detecting Aβ and Tau peptides, are among the only one available. Peripheral biomarkers, such as blood, have all failed to show consistency. However, it has been shown that Aβ peptide is able to leave the brain toward the blood system and is then transported to peripheral organ. The mechanism by which the peptide is cleared from peripheral organs is not completely known yet, but one hypothesis is that it is partly eliminated by bile excretion in the stools. Objectives and methods: The study consists of detection and quantification of Aβ42 peptide in the stools of people suffering from AD and control non-demented individuals. The objective is to evaluate a new tool that should allow diagnosis or screening of AD in waste products. We analyzed amyloid levels in stools of 9 subjects with AD and 9 non-demented age-matched control subjects. We also exposed stool amyloid levels detected in 4 amyloid-depositing transgenic mice expressing AD, APPPS1 mice. Detection and quantification of Aβ42 peptide were performed using a sandwich ELISA technique. Results: Fecal Aβ42 levels tend to be higher in Alzheimer’s subjects compared to control subjects (mean value 14.54 ng/l and 10.10 ng/l respectively, AD to control ratio 1.44, p = 0.015), in dementia subjects compared to MCI subjects (mean value 16.8 ng/l and 12.74 ng/l respectively, p = 0.254), in dementia subjects compared to control subjects (p = 0.011) and in MCI subjects compared to control subjects (p = 0.156). Every correlation analysis made did not show any significant results. Discussion: In this study, we showed that detection of Aβ42 peptide in human stools using ELISA technique was possible and that Aβ42 rates were higher in AD subjects than control individuals without significant brain amyloidosis (AD to control ratio 1.44). However, larger scales studies are needed to confirm those results and to evaluate the correlation between fecal Aβ levels and other clinical or biological biomarkers of AD. Nevertheless, the use of stool as a diagnostic tool for AD is promising. Yet, due to difficulties concerning the stool harvest process in relation to cognitive impairment, this test could only be offered to early stage Alzheimer’s patients (MCI stage) or be performed by caregivers in institutionalized subjects in a medico-social institution.