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

Identification de Biomarqueurs Diagnostiques Dans Les Larmes de Patients Atteints de Maladie d'Alzheimer : l'étude Pilote COG-EYE

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Victoire LEROY, MD; Phone Number: 0247477693; Email: victoire.leroy@univ-tours.fr
• Study Contact Backup: Name: Raoul Kanav KHANNA, MD, PhD; Email: raoul.khanna@univ-tours.fr

Study Locations

• France
  • France
    • Tours, France, France, 37044
      • Recruiting
      • CHRU de Tours
      • Principal Investigator: Victoire LEROY, MD
      • Contact: Victoire LEROY; Phone Number: +332 47 47 76 93; Email: victoire.leroy@univ-tours.fr
      • Contact: Coralie TAILLEBUIS; Phone Number: +332 47 47 39 09; Email: cpcq@chu-tours.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients with AD dementia; 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); 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
Active Comparator: Patients with AD Mild Cognitive Impaiment (MCI); 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); 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; Other: Collection of a blood sample (5 mL) for blood biomarkers analysis; Collection of a blood sample (5 mL) for blood biomarkers analysis.
Sham Comparator: Healthy controls; 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); 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of total Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI	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 phosphylated Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI	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	A inclusion
Concentration of Amyloid β 1-40 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI	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	A inclusion
Concentration of Amyloid β 1-42 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI	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	A inclusion
Lipids in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI	Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of lipids in basal tears using liquid chromatography-mass spectrometry.	At inclusion
Metabolites in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI	Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of metabolites in basal tears using liquid chromatography-mass spectrometry.	At inclusion
Concentration of total Tau proteins in basal tears of patients with AD-dementia vs patients with AD-MCI	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-dementia vs patients with AD-MCI	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-dementia vs patients with AD-MCI	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 proteins in basal tears of patients with AD-dementia vs patients with AD-MCI	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-dementia vs patients with AD-MCI	Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of lipids in basal tears using liquid chromatography-mass spectrometry.	At inclusion
Metabolites in basal tears of patients with AD-dementia vs patients with AD-MCI	Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of metabolites in basal tears using liquid chromatography-mass spectrometry.	At inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Study Director: Victoire LEROY, MD, CHRU de Tours

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: biomarkers; Alzheimer disease; tears; metabolomic; lipidomic
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Lacerations; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Microtubule Proteins; Cytoskeletal Proteins; Microtubule-Associated Proteins; tau Proteins
• Other Study ID Numbers: DR240140

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may obtain access to all deidentified data in COG-EYE on a substantial request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No