Validation of an Alzheimer's Disease Marker by Fecal Assay of Amyloid Peptides and Tau Proteins

NCT06481878 | Recruiting

• 2 other identifiers: 38RC24.00262024-A00378-39
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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).

  Between inclusion and Month 6

Secondary Outcomes (3)

• 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+).

  between Month 6 and Month 12

• Follow the efficacy of a treatment if the AD TCm (A+ T+) subject takes one

  between Month 6 and Month 12

• Observe the evolution and kinetics of AD biomarkers in subjects without Alzheimer's disease at the stage of minor cognitive impairment (TCm LCRdiscordant).

  between Month 6 and Month 12

Study Arms (5)

35 MA TCM (A+ T+)

Group of patients with established Alzheimer's disease at the stage of major cognitive impairment

Diagnostic Test: faecal analysis

15 MA TCm (A+ T+)

Group of patients with established Alzheimer's disease at the stage of minor cognitive impairment

Diagnostic Test: faecal analysis

15 TC Non MA LCR negatif (A- T-)

Group of patients with minor or major cognitive impairment but without AD

Diagnostic Test: faecal analysis

15 TCm LCRdiscordant (A+ T-) ou (A- T+)

Group of patients with minor cognitive impairment and discordant CSF

Diagnostic Test: faecal analysis

35 VS

Group of healthy volunteers

Diagnostic Test: faecal analysis

Interventions

faecal analysis DIAGNOSTIC_TEST

Collection of medical data and stool sampling

15 MA TCm (A+ T+); 15 TC Non MA LCR negatif (A- T-); 15 TCm LCRdiscordant (A+ T-) ou (A- T+); 35 MA TCM (A+ T+); 35 VS

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Single-center study, recruitment among patients consulting the CMRR of the Alpine arc

You may qualify if:

• For subjects with Alzheimer's disease MA TCM (A+ T+):
• 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
• No informed opposition
• For subjects with AD TCm (A+ T+):
• Subject diagnosed with AD according to IWG 2021 criteria
• Subject at the stage of minor cognitive impairment
• Minimum age 40
• No informed opposition For subjects with minor or major cognitive impairment who do not have AD TC Non-AD LCR negative (A- T-)
• Subject at stage of minor or major cognitive impairment
• CSF negative (A-T-) for Alzheimer's disease biomarkers: A-T- according to ATN classification
• Minimum age 40
• No informed objection and TCm CSFdiscordant (A+ T-) or (A- T+):

You may not qualify if:

• For MA TCM (A+ T+), MA TCm (A+T+) and TC Non MA LCR negatif (A-T-) and TCm LCRdiscordant (A+ T-) or (A- T+):
• 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)
• For healthy volunteers:
• Incapacity to understand research instructions or to give informed non-opposition
• Persons covered by articles L1121-5 to L1121-8 of the CSP (legally protected adult, subject under administrative or judicial supervision)
• Absence of social security affiliation or of such a scheme

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

Grenoble Alpes University Hospital

Grenoble, 38043, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Feces

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Occult Blood

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Mathilde SAUVEE

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mathilde SAUVEE

CONTACT

33 (0)4 76 76 57 90; MSauvee@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: July 1, 2024
• Study Start: October 11, 2024
• Primary Completion (Estimated): October 6, 2027
• Study Completion (Estimated): October 6, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

FR (1)