Tanycytes in Alzheimer's Disease and Frontotemporal Dementia

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

Interventions

BIOLOGICAL

Lumbar puncture

5 mL of CSF

BIOLOGICAL

blood sample

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

Sponsors & Collaborators

• European Research Council

  collaborator OTHER

• CH Calais

  collaborator UNKNOWN

• Centre Hospitalier VALENCIENNES

  collaborator OTHER

• Région Nord-Pas de Calais, France

  collaborator OTHER

• Centre Hospitalier de Bethune

  collaborator NETWORK

• University Hospital, Lille

  lead OTHER

Principal Investigators

• Thibaud LEBOUVIER, MD,PhD · University Hospital, Lille

Eligibility

Min Age

40 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-09-06

Primary Completion

2026-10-31

Completion

2026-10-31

Countries

• France

Study Locations