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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Concentration of total Tau proteins in basal tears of patients with AD vs healthy volunteers [Time frame: At inclusion]
• Concentration of phosphorylated Tau proteins in basal tears of patients with AD vs healthy volunteers [Time frame: At inclusion]
• Concentration of Amyloid β 1-40 proteins in basal tears of patients with AD vs healthy volunteers [Time frame: At inclusion]
• Concentration of Amyloid β 1-42 in basal tears of patients with AD vs healthy volunteers [Time frame: At inclusion]
• Lipids in basal tears of patients with AD vs healthy volunteers [Time frame: At inclusion]
• Metabolites in basal tears of patients with AD vs healthy volunteers [Time frame: At inclusion]

Secondary outcome measures (12)

• Concentration of total Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI [Time frame: At inclusion]
• Concentration of phosphylated Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI [Time frame: A inclusion]
• Concentration of Amyloid β 1-40 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI [Time frame: A inclusion]
• Concentration of Amyloid β 1-42 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI [Time frame: A inclusion]
• Lipids in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI [Time frame: At inclusion]
• Metabolites in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI [Time frame: At inclusion]
• Concentration of total Tau proteins in basal tears of patients with AD-dementia vs patients with AD-MCI [Time frame: At inclusion]
• Concentration of phosphorylated Tau proteins in basal tears of patients with AD-dementia vs patients with AD-MCI [Time frame: At inclusion]
• Concentration of Amyloid β 1-40 proteins in basal tears of patients with AD-dementia vs patients with AD-MCI [Time frame: At inclusion]
• Concentration of Amyloid β 1-42 proteins in basal tears of patients with AD-dementia vs patients with AD-MCI [Time frame: At inclusion]
• Lipids in basal tears of patients with AD-dementia vs patients with AD-MCI [Time frame: At inclusion]
• Metabolites in basal tears of patients with AD-dementia vs patients with AD-MCI [Time frame: At inclusion]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 1 center

• CHRU de Tours — Tours

Identifiers

NCT: NCT06661564 · DR240140

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗