Alzheimer Disease
Conditions
Keywords
biomarkers, tears, metabolomic, lipidomic, Alzheimer disease
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.
Interventions
OTHERBasal 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
OTHERCollection of a blood sample (5 mL) for blood biomarkers analysis
Collection of a blood sample (5 mL) for blood biomarkers analysis.
Sponsors
University Hospital, Tours
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of total Tau proteins in basal tears of patients with AD vs healthy volunteers | At inclusion | 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 |
| Concentration of phosphorylated Tau proteins in basal tears of patients with AD vs healthy volunteers | At inclusion | 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 |
| Concentration of Amyloid β 1-40 proteins in basal tears of patients with AD vs healthy volunteers | At inclusion | 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 |
| Concentration of Amyloid β 1-42 in basal tears of patients with AD vs healthy volunteers | At inclusion | 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 |
| Lipids in basal tears of patients with AD vs healthy volunteers | At inclusion | Collection of tears (5μL) using a glass micropipette without local anaesthetic. Lipids in tears of patients with AD vs healthy volunteers |
| Metabolites in basal tears of patients with AD vs healthy volunteers | At inclusion | Collection of tears (5μL) using a glass micropipette without local anaesthetic. Metabolites in tears of patients with AD vs healthy volunteers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of total Tau proteins in basal tears of patients with AD-dementia vs patients with AD-MCI | At inclusion | 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 |
| Concentration of phosphorylated Tau proteins in basal tears of patients with AD-dementia vs patients with AD-MCI | At inclusion | 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 |
| Concentration of Amyloid β 1-40 proteins in basal tears of patients with AD-dementia vs patients with AD-MCI | At inclusion | 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 |
| Concentration of total Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI | At inclusion | 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 |
| Lipids in basal tears of patients with AD-dementia vs patients with AD-MCI | At inclusion | Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of lipids in basal tears using liquid chromatography-mass spectrometry. |
| Metabolites in basal tears of patients with AD-dementia vs patients with AD-MCI | At inclusion | Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of metabolites in basal tears using liquid chromatography-mass spectrometry. |
| Concentration of Amyloid β 1-42 proteins in basal tears of patients with AD-dementia vs patients with AD-MCI | At inclusion | 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 |
| Concentration of phosphylated Tau proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI | A inclusion | 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 |
| Concentration of Amyloid β 1-40 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI | A inclusion | 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 |
| Concentration of Amyloid β 1-42 proteins in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI | A inclusion | 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 |
| Lipids in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI | At inclusion | Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of lipids in basal tears using liquid chromatography-mass spectrometry. |
| Metabolites in tears vs plasma and Cerebral spinal fluid (CSF) within patients with AD-MCI | At inclusion | Collection of tears (5μL) using a glass micropipette without local anaesthetic. Identification of metabolites in basal tears using liquid chromatography-mass spectrometry. |
Countries
France
Contacts
Primary ContactVictoire LEROY, MD
Backup ContactRaoul Kanav KHANNA, MD, PhD
Outcome results
None listed