Ectosomes, New Biomarkers of Tau Pathology?

NCT03381482 | Completed

• 2 other identifiers: 2016_592017-A01715-48
• Study Type: observational
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

In Alzheimer's disease (AD), neurofibrillary degeneration (NFD) is characterized by the intraneuronal aggregation of Tau proteins. The pathology progresses through a hierarchical pathway that may be associated with the intercellular transmission of pathology as demonstrated in our rat models. This transmission implies that Tau is actively secreted and may participate to the first steps of Tau pathology spreading. It is demonstrated in cell lines and animal models (rodents and non-human primates) that Tau is secreted not only in free forms but also in extracellular vesicles. If Tau is found in biological fluids before neuronal death it may represent an early marker of the NFD and will also define therapeutically targets. In this context, the aim is now to transfer this knowledge in humans and to decipher the nature of Tau secreted in plasma and cerebrospinal fluids collected from healthy controls to AD patients, and to decipher if the presence of tau inside vesicles is influenced by the pathology.

Conditions

Alzheimer Disease

Keywords

Alzheimer disease; Extracellular vesicles; Biomarker; Tau; CSF; Plasma

Outcome Measures

Primary Outcomes (1)

• Presence of Tau in extracellular vesicles in CSF

  Tau will be measured by ELISA in extracellular vesicles and the presence of Tau in extracellular vesicles will considered positive if the concentration of Tau is superior to the sensitivity threshold of the antibody used.

  Baseline

Secondary Outcomes (2)

• The ratio of free Tau/vesicular Tau for all groups will be assessed with samples obtained during the visit.

  Baseline

• The presence of clusters of the epigenetic markers H3K9me3 in nuclei of peripheral blood mononuclear cells for all groups will be assessed with samples obtained during the visit.

  Baseline

Study Arms (5)

Controls

Group 1: the 4ml of CSF collected in the surgery context will be kept for the study, and 6x5ml of blood will be added to the usual samples.

Diagnostic Test: CSF drawing during spinal anaesthesia; Diagnostic Test: Fasting blood sample

Asymptomatic cases with high risk to develop AD

Group 2: 10ml of CSF and 6x5ml of blood will be collected

Diagnostic Test: Fasting blood sample; Diagnostic Test: Lumbar puncture

Cases with isolated cognitive complaint

Group 3: 10ml of CSF and 6x5ml of blood will be collected

Diagnostic Test: Fasting blood sample; Diagnostic Test: Lumbar puncture

Prodromal AD

Group 4: 10ml of CSF and 6x5ml of blood will be collected

Diagnostic Test: Fasting blood sample; Diagnostic Test: Lumbar puncture

Mild to moderate probable AD-type dementia

Group 5: 10ml of CSF and 6x5ml of blood will be collected

Diagnostic Test: Fasting blood sample; Diagnostic Test: Lumbar puncture

Interventions

CSF drawing during spinal anaesthesia DIAGNOSTIC_TEST

4mL of CSF by lumbar puncture

Controls

Fasting blood sample DIAGNOSTIC_TEST

6x5 mL of fasting blood sample

Asymptomatic cases with high risk to develop AD; Cases with isolated cognitive complaint; Controls; Mild to moderate probable AD-type dementia; Prodromal AD

Lumbar puncture DIAGNOSTIC_TEST

10 mL of CSF by lumbar puncture

Asymptomatic cases with high risk to develop AD; Cases with isolated cognitive complaint; Mild to moderate probable AD-type dementia; Prodromal AD

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects intended to participate in group 1 have to undergo a lumbar puncture for other reasons than a cognitive complaint. They will be identified in the anaesthesiology department among patients who are waiting for scheduled orthopaedic surgery needing spinal anaesthesia. They will have the sample collection done with its specific procedures in the same time. if a subject is already followed at the MRRC and meets group 1 eligibility criteria, he/she could be asked to participate in the study and thus be enrolled and followed by a MRRC investigator. Patients intended to participate in groups 2 to 5 will be identified at the MRRC during their scheduled visit with the investigators specialized in neurology/geriatric medicine.

You may qualify if:

• Subjects able to undergo a lumbar puncture;
• Subjects who have a partner who will be required for driving back the subject after the lumbar punction for safety reasons (not required for control subjects);
• Subjects (or the study partner for group 5) capable of and willing to comply with the protocol and to give their written informed consents after having received and understood the subject information. According to the legal protection or the mental capacities of the subject, he/she will be accompanied by him/her legally acceptable representative during this procedure;
• Blood coagulation testing
• Subjects registered with the French Social Security, in agreement with the French law on biomedical experimentation.
• Group 1: controls
• absence of cognitive complaint
• absence of significant cognitive impairment: MMSE\>27
• Negative ApoE4 status (ε 4-/ ε 4-) No family history of AD at first degree Group 2: asymptomatic cases with high risk to develop AD
• absence of cognitive complaint
• absence of significant cognitive impairment : MMSE\>27
• known ApoE4 status or family history of AD at first degree Group 3: cases with isolated cognitive complaint
• presence of a cognitive complaint
• absence of cognitive impairment assessed by MMSE\>27 and standard neuropsychological examination (performed \< 1 year) Group 4: prodromal AD according to the 2007 criteria (Dubois et al., 2007)
• progressive and significant episodic memory impairment \>6 months

You may not qualify if:

• Subjects with dementia caused by a non-neurodegenerative disease, including patients with severe cerebrovascular risk factor load;
• Associated Illnesses or conditions:
• Subjects with other neurodegenerative disease such as fronto-temporal dementia (FTD), Lewy body dementia and Parkinson's disease;
• Subjects with other serious neurological disorder such as brain tumour, stroke, epilepsy, hydrocephalus and any condition which contraindicates, in the investigator's judgment, entry to the study;
• Subjects with demyelinating diseases of the peripheral nervous system such as Guillain-Barre Syndrome;
• Subjects with known active Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV);
• Subjects with clinical or significant laboratory abnormalities, in the judgment of the investigator;
• Others:
• Subjects with excessive alcohol intake or drug abuse, in the judgment of the investigator;
• Subjects who have contraindications to perform a lumbar puncture;
• Subjects who, in the opinion of the Investigator, have a risk of non-compliance to the study procedures or who are otherwise not appropriate to include in this clinical trial (for example, being impossible to contact in case of emergency).

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

Hôpital Roger Salengro, CHRU

Lille, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood and CSF sampling

MeSH Terms

Conditions

Alzheimer Disease; Pick Disease of the Brain

Interventions

Spinal Puncture

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Vincent DERAMECOURT, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 22, 2017
• Study Start: December 20, 2017
• Primary Completion: December 21, 2022
• Study Completion: December 23, 2022
• Last Updated: August 20, 2025

Record last verified: 2025-08

Locations

FR (1)