Alzheimer's disease (AD) is the leading cause of dementia in humans, currently affecting almost one million people in France. It results from an irreversible degeneration of neurons responsible for a progressive decline in the main cognitive and memory functions due to a cerebral accumulation of plaques containing fibrillary amyloid peptide (Aβ) and neurofibrillary tangles composed of truncated, hyperphosphorylated tau protein (pTau).
There is currently no curative treatment for this disease in France. However, two treatments aimed at reducing beta-amyloid plaques in the brain have been approved by the U.S. Food and Drug Administration. The failure of the latest therapeutic strategies is largely due to the fact that the disease is diagnosed too late, starting with a long asymptomatic phase, which is the one that needs to be targeted in order to prevent irreversible neurodegenerative mechanisms.
The development of diagnostic tools is gradually making it possible to detect such a sequence, but this has its drawbacks (radioactive load, invasive procedure, cumbersome set-up).
Over the last ten years, research has focused on the development of plasma or salivary markers. Although encouraging, these studies show either a lack of sensitivity or reproducibility, or a lack of specificity or precocity.
The expression of Aβ and Tau proteins has recently been demonstrated in the enteric nervous system and enterocytes. Intestinal Aβ is involved in various gut functions and regulation.
What recent work by investigators demonstrates is the essential and hitherto unrecognized role of the gut-brain axis in maintaining brain homeostasis. In a mouse model of AD, the investigators have demonstrated a mechanism for intestinal elimination (clearance) of toxic brain forms of Tau and Aβ proteins, via the lymphatic network.
The clearance of cerebral Tau and Aβ proteins in the stool may constitute a reliable and powerful diagnostic signature of AD. Its study would represent a new, non-invasive and easily accessible technique for the early diagnosis of AD in humans.
Subjects diagnosed with AD according to IWG 2021 criteria
Subject at the stage of major cognitive impairment
At least 40 years of age
Presence of a caregiver or support person
Inability to understand search instructions or to give informed non-opposition
Absence of social security affiliation or plan
Persons covered by articles L1121-5 to L1121-8 of the CSP (legally protected adult, subject under administrative or judicial supervision)
Incapacity to understand research instructions or to give informed non-opposition
Single-center study, recruitment among patients consulting the CMRR of the Alpine arc
Cohort
Prospective
faecal analysis
Diagnostic testCollection of medical data and stool sampling
to determine the amount of fibrillar and oligomeric amyloid peptide and phosphorylated tau protein measured in the stools of subjects issued as soon as possible after recruitment
Quantity of AD biomarkers in stool. The biomarkers studied will be : In Lumipulse (CHUGA platform): beta-amyloid 42,beta-amyloid 40, Ptau and total tau. Dotblot (GIN): Soluble forms of phosphorylated tau (Tau-pThre205, Tau-pThre181, Tau-pThre217, Tau-pser404) or total tau (panTau), as well as toxic oligomeric forms of the beta-amyloid peptide (E22P). Finally, insoluble fibrillar forms of Tau (AT8) and beta-amyloid peptide (OC).
To observe the evolution and kinetics of AD biomarkers in subjects with Alzheimer's disease at the stage of minor cognitive impairment (AD TCm A+ T+).
Quantity of AD biomarkers in the stool of subjects with Alzheimer's disease at the TCm stage between M6 and M12 (AD TCm A+ T+)
Follow the efficacy of a treatment if the AD TCm (A+ T+) subject takes one
Increase or decrease in the quantity of AD biomarkers in the stool of subjects with Alzheimer's disease at the TCm stage under treatment between M6 and M12 (AD TCm A+ T+).
Observe the evolution and kinetics of AD biomarkers in subjects without Alzheimer's disease at the stage of minor cognitive impairment (TCm LCRdiscordant).
Quantity of AD biomarkers in the stool of non-Alzheimer's subjects at stage TCm CSFdiscordant) between M6 and M12
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