Tanycytes in Alzheimer's Disease and Frontotemporal Dementia

NCT05288842 | Recruiting

• 2 other identifiers: 2020_262021-A00879-32
• Study Type: observational
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic and hormonal deregulations are both a risk factor and a hallmark of Alzheimer's disease (AD) and frontotemporal dementia (FTD), occurring early in the course of the disease. In FTD in particular, hyperorality and dietary changes are associated with metabolic and hormonal changes such as altered levels of the anorexigenic hormone leptin. The hypothalamus is a brain region that controls metabolism and hormonal systems. Hypothalamic function depends on its ability to sense peripheral signals. The hypothalamus sits on a circumventricular organ called the median eminence (ME) that puts it in contact with systemic blood circulation. In the ME, fenestrated capillaries allow the diffusion of bloodborne factors. However, despite the lack of blood-brain barrier at brain microvessels, diffusion is controlled by specialized ependymoglial cells, the tanycytes, which exert a barrier function between the ME and the third ventricle and controls the access of blood-borne molecules into the hypothalamus. Previous work from our laboratory and the ERC consortium has highlighted the role of tanycytes not only in the regulation of the release of neurohormones from neuroendocrine nerve terminals into the pituitary portal blood circulation, but also in the transport of circulating leptin into the hypothalamus. Hence hypothalamic dysfunction in AD and FTD can result either from dysregulation of neuroendocrine secretions, direct neuronal loss or from defective transport (and hence resistance) to hormones like leptin. This study is to demonstrate that leptin transport though tanycytes is early altered in FTD and AD and correlates

Conditions

Alzheimer Disease; Frontotemporal Dementia

Keywords

Alzheimer disease; Frontotemporal Dementia; tanycytes; metabolism; hormone; cerebrospinal fluid; blood; hypothalamus

Outcome Measures

Primary Outcomes (1)

• Mean CSF-to-blood ratio (CBR) of leptin concentration.

  Leptin concentration in blood and CSF (in the pg/mL range) will be measured by enzyme-linked immunosorbent assay (ELISA).

  At visit 2, occurring 1 to 90 days after visit 1(Baseline)

Secondary Outcomes (10)

• Mean of the CSF-to-blood ratio (CBR) of hypothalamus-related hormones

  At visit 2, occurring 1 to 90 days after visit 1(Baseline)

• Blood metabolomics

  At visit 2, occurring 1 to 90 days after visit 1(Baseline)

• CSF metabolomics

  At visit 2, occurring 1 to 90 days after visit 1(Baseline)

• Correlation coefficient between leptin CBR and general cognitive functioning assessed by the Mattis Dementia Rating Scale (MDRS)6

  At visit 2, occurring 1 to 90 days after visit 1(Baseline)

• Correlation coefficients between leptin CBR and performances in a neuropsychological battery assessing the function of affective and social cognition in each AD and FTD groups

  At visit 2, occurring 1 to 90 days after visit 1(Baseline)

Study Arms (3)

Group 1: Controls

Biological: Lumbar puncture; Biological: blood sample

Group 2: Alzheimer's Disease

Biological: Lumbar puncture; Biological: blood sample

Group 3: Frontotemporal Dementia

Biological: Lumbar puncture; Biological: blood sample

Interventions

Lumbar puncture BIOLOGICAL

5 mL of CSF

Group 1: Controls; Group 2: Alzheimer's Disease; Group 3: Frontotemporal Dementia

blood sample BIOLOGICAL

6x5 mL of blood sample collected :1 dry tube, 2 EDTA tubes, 1 fluoride tube, and 2 polypropylene tubes

Group 1: Controls; Group 2: Alzheimer's Disease; Group 3: Frontotemporal Dementia

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects intended to participate will be recruited in Lille in the memory clinic and in the memory clinic network Meotis (North of France above Paris)

You may qualify if:

• Subjects able to undergo a lumbar puncture
• Subjects registered with the French Social Security, in agreement with the French law on biomedical experimentation
• To be assigned in the study subgroups, subjects will have to fulfill the specific following criteria:
• Group 1: Controls
• absence of cognitive complaint (completion of the memory complaint questionnaire)
• absence of significant cognitive impairment: normal MMSE according to age and education levels
• Subjects capable of and willing to comply with the protocol and to give their written informed consents after having received and understood the subject information Group 2: Alzheimer's Disease
• Diagnosis of probable Alzheimer's disease dementia according to the NIA 2011 criteria1
• MMSE ≥ 16
• Subjects who have a study partner. The study partner is required to complete several scales and to drive back the subject after the lumbar puncture for safety reasons. If the subjects or their study partners are not able to drive, their transport fees will be reimbursed by the promotor
• Subjects and study partners 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, the subject will be accompanied by a legally acceptable representative during this procedure Group 3: Frontotemporal Dementia
• Diagnosis of probable frontotemporal dementia according to the FTDC 2011 criteria2
• MMSE ≥ 16
• Subjects who have a study partner. The study partner is required to complete several scales and to drive back the subject after the lumbar puncture for safety reasons. If the subjects or their study partners are not able to drive, their transport fees will be reimbursed by the promotor
• Subjects and study partners 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, the subject be accompanied by a legally acceptable representative during this procedure

You may not qualify if:

• Subjects with dementia caused by a non-neurodegenerative disease, including patients with severe cerebrovascular risk factor load
• Subjects who have contraindications to perform a lumbar puncture
• Subjects who have contraindications to perform a MRI scan
• Weighted less than 45 kg
• Associated illnesses or conditions:
• Subjects with other neurodegenerative disease such as Lewy body dementia and Parkinson's disease
• Subjects with other serious neurological disorder such as brain tumor, stroke, epilepsy, hydrocephalus and any condition which contraindicates, in the investigator's judgment, entry to the study;
• Subjects with severe metabolic or endocrine disorder (excluding hypothyroidism under stable hormone replacement therapy, controlled type 2 diabetes or common dyslipidaemia), previously known or identified at screening
• Subjects under metformin treatment.
• Subjects with known active HCV, HBV or HIV
• Subjects with clinical or significant laboratory abnormalities, previously known or identified at screening, in the judgment of the investigator
• Others:
• Pregnancy or breastfeeding or Women of childbearing age without effective contraception (a pregnancy test will be done)
• Subjects with excessive alcohol intake or drug abuse, in the judgment of the investigator
• 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
• European Research Council: collaborator
• CH Calais: collaborator
• Centre Hospitalier VALENCIENNES: collaborator
• Région Nord-Pas de Calais, France: collaborator
• Centre Hospitalier de Bethune: collaborator

Study Sites (1)

Memory Resources and Research Center Lille

Lille, 59037, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma and CSF supernatant will be aliquoted and labelled for storage

MeSH Terms

Conditions

Alzheimer Disease; Frontotemporal Dementia

Interventions

Spinal Puncture; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

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

• Thibaud LEBOUVIER, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thibaud LEBOUVIER, MD,PhD

CONTACT

0320445962; thibaud.lebouvier@chru-lille.fr

Study Design

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

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: March 21, 2022
• Study Start: September 6, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 14, 2025

Record last verified: 2025-05

Locations

FR (1)