Tanycytes in Alzheimer's Disease and Frontotemporal Dementia

Recruiting now

Conditions studied: Alzheimer Disease, Frontotemporal Dementia

In brief

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

Key facts

Study ID: NCT05288842
Run by: University Hospital, Lille
People needed: 102
Starts: 2022-09-06
Expected to finish: 2026-10-01
Last updated by the study team: 2026-05-18

Who can join

Age: 40 and older, up to 85. Sex: any. Healthy volunteers: accepted.

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…

General exclusion criteria:
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.
Biological exclusion criteria:
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)

Where it is running

Memory Resources and Research Center Lille — Lille, France (enrolling)

Full record on ClinicalTrials.gov

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