Identification of Diagnosis Biomarkers in the Tears of Alzheimer's Disease Patients: The COG-EYE Pilot Study

NCT06661564 | Recruiting

• 1 other identifier: DR240140
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The diagnosis of Alzheimer's disease (AD) relies on the detection of protein biomarkers, particularly in cerebrospinal fluid (e.g., Aβ and phosphorylated Tau) or through brain imaging. The invasive nature of lumbar puncture and the numerous contraindications have driven the search for early and reliable diagnostic biomarkers for AD. Human tears are an accessible biological fluid that has proven relevant in the biomarker search strategy for both ophthalmological and systemic diseases, especially neurodegenerative conditions. Advances in methods for low-volume analysis have facilitated the identification of tear biomarkers. Total tau has been reported as elevated in the tears of patients with AD compared to controls (n=65). Additionally, metabo-lipidomic analyses offer several advantages (accessibility, non-invasiveness, reproducibility) and also appear promising as a diagnostic tool for systemic and neurodegenerative diseases, such as amyotrophic lateral sclerosis. This supports the relevance of comparing both AD proteins biomarkers and metabo-lipidomic signatures in the tears of patients with AD (Mild Cognitive Impairement (MCI) and dementia) with healthy controls.

Conditions

Alzheimer Disease

Keywords

biomarkers; tears; metabolomic; lipidomic; Alzheimer disease

Outcome Measures

Primary Outcomes (6)

• Concentration of total Tau proteins in basal tears of patients with AD vs healthy volunteers

  12μL of tears will be collected using Schirmer strips after instillation of an anaesthetic eye drop. A multiplex analysis for the detection of protein of interest

  At inclusion

• Concentration of phosphorylated Tau proteins in basal tears of patients with AD vs healthy volunteers

  12μL of tears will be collected using Schirmer strips after instillation of an anaesthetic eye drop. A multiplex analysis for the detection of protein of interest

  At inclusion

• Concentration of Amyloid β 1-40 proteins in basal tears of patients with AD vs healthy volunteers

  12μL of tears will be collected using Schirmer strips after instillation of an anaesthetic eye drop. A multiplex analysis for the detection of protein of interest

  At inclusion

• Concentration of Amyloid β 1-42 in basal tears of patients with AD vs healthy volunteers

  12μL of tears will be collected using Schirmer strips after instillation of an anaesthetic eye drop. A multiplex analysis for the detection of protein of interest

  At inclusion

• Lipids in basal tears of patients with AD vs healthy volunteers

  Collection of tears (5μL) using a glass micropipette without local anaesthetic. Lipids in tears of patients with AD vs healthy volunteers

  At inclusion

• Metabolites in basal tears of patients with AD vs healthy volunteers

  Collection of tears (5μL) using a glass micropipette without local anaesthetic. Metabolites in tears of patients with AD vs healthy volunteers

  At inclusion

Secondary Outcomes (12)

• Concentration of total Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI

  At inclusion

• Concentration of phosphylated Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI

  A inclusion

• Concentration of Amyloid β 1-40 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI

  A inclusion

• Concentration of Amyloid β 1-42 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI

  A inclusion

• Lipids in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI

  At inclusion

Study Arms (3)

Patients with AD dementia

ACTIVE COMPARATOR

Patient ≥ 18 years old with AD at a major stage according to the 2018 NIA-AA criteria (dementia)

Other: Basal tear collection for the analysis of metabo-lipidomic profiles and concentrations of protein biomarkers (Tau, phosphorylated Tau, Aβ 1-40, and Aβ 1-42)

Patients with AD Mild Cognitive Impaiment (MCI)

ACTIVE COMPARATOR

Patient ≥ 18 years old with AD at a minor stage according to the 2018 NIA-AA criteria (Mild Cognitive Impairment)

Other: Basal tear collection for the analysis of metabo-lipidomic profiles and concentrations of protein biomarkers (Tau, phosphorylated Tau, Aβ 1-40, and Aβ 1-42); Other: Collection of a blood sample (5 mL) for blood biomarkers analysis

Healthy controls

SHAM COMPARATOR

Participants ≥ 18 years old with no known central neurological pathology, no cognitive decline, and matched by age (± 2 years) and sex with a patient from AD-MCI group

Other: Basal tear collection for the analysis of metabo-lipidomic profiles and concentrations of protein biomarkers (Tau, phosphorylated Tau, Aβ 1-40, and Aβ 1-42)

Interventions

Basal tear collection for the analysis of metabo-lipidomic profiles and concentrations of protein biomarkers (Tau, phosphorylated Tau, Aβ 1-40, and Aβ 1-42) OTHER

Collection of a tear volume of (i) 2 x 5µL using glass microcapillary tubes and (ii) 12µL using Schirmer strips after the instillation of anesthetic eye drops for metabo-lipidomic analysis and multiplexing of protein markers

Healthy controls; Patients with AD Mild Cognitive Impaiment (MCI); Patients with AD dementia

Collection of a blood sample (5 mL) for blood biomarkers analysis OTHER

Collection of a blood sample (5 mL) for blood biomarkers analysis.

Patients with AD Mild Cognitive Impaiment (MCI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Participant affiliated in French Social Security scheme
• Informed and written consent from the participant

You may not qualify if:

• Pregnant or breastfeeding woman
• Participant under judicial protection measures
• Participant under guardianship or curatorship
• Contraindications to participation in the research:
• Other neurodegenerative disease Any eye drops or treatment that may interfere with tear production Occasional or permanent contact lens use within the last 3 months Eye surgery ≤3 months Any ocular pathology other than refractive errors, oculomotor disorders, amblyopia Any general pathology other than AD with ocular implications
• Inability to perform tear collection

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (1)

CHRU de Tours

Tours, France, 37044, France

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Lacerations

Interventions

tau Proteins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Microtubule-Associated Proteins; Microtubule Proteins; Cytoskeletal Proteins; Proteins; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins

Study Officials

• Victoire LEROY, MD

  CHRU de Tours

  STUDY DIRECTOR

Central Study Contacts

Victoire LEROY, MD

CONTACT

0247477693; victoire.leroy@univ-tours.fr

Raoul Kanav KHANNA, MD, PhD

CONTACT

raoul.khanna@univ-tours.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2024
• First Posted: October 28, 2024
• Study Start: July 9, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)