NCT03378453

Narcolepsy Protect Against Alzheimer's Disease?

Narcolepsy Protect Against Alzheimer's Disease? Protective Role of Low Rates of Orexin on the Occurrence of Intracerebral Amyloid Deposits Characteristic of the Alzheimer's Disease: A Pilot Study

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 38 (actual)
• Sponsor: University Hospital, Montpellier · Academic / Other
• Sex: All
• Age: 65 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Links between orexin and amyloid processes have been underlined recently. During the Alzheimer's process an upregulation of the orexin mechanism has been observed. The pathophysiological mechanism of narcolepsy type 1 is linked to orexin deficiency. Thus, the investigators hypothesized that patients with narcolepsy may be protected from amyloid brain lesions, hallmarks of the Alzheimer's process. To test this hypothesis, the investigators analyzed the brain amyloid load measured by PET-scan amyloid brain imaging in patients with narcolepsy type 1 compared to controls without cognitive deficits.

Detailed description

The lack of innovative treatments in Alzheimer' disease (AD) is due to the non-understanding of the pathological process. The investigators need to include the latest concept of the sleep-wake/circadian kinetics of proteins in the brain, the new theory of the wash-out of pathological proteins via the brain glymphatic system during sleep and act at an early stage. New pathways are opened to better understand proteinopathies' processes and to propose new therapeutics interventions. The variations of the production/clearance curves of amyloid in the cerebrospinal fluid (CSF) during circadian rhythms and sleep-wake cycles have been demonstrated in in vivo metabolism experimentations. Suprachiasmatic nucleus damages due to AD may induce circadian regulation dysfunction and secondary sleep/wake cycle alterations. Key sleep/wake cycle neuromediators (Orexin-A, melatonin) are involved in the regulation of brain amyloid levels. The influence of orexin-A signaling on Aβ metabolism in animals and humans was recently highlighted. In rats, orexin-A release shows a 24-h fluctuation similar to that of brain interstitial fluid Aβ. In transgenic mice that overexpress amyloid precursor protein (APP), brain interstitial fluid Aβ concentration increases during wakefulness and after orexin-A infusion. Conversely, it decreases during sleep and after infusion of an orexin-A receptor antagonist6. In transgenic mice that overexpress APP/presenilin1 (PS1), in which the orexin gene is knocked out, a reduction of Aβ pathology was found, possibly caused by changes in sleep time. Orexin-A is linked to Aβ42 in AD and an increase of CSF orexin-A is observed in AD vs. controls, possibly related to sleep deterioration and neurodegeneration. The narcolepy with cataplexy type 1 is the only disease with a specific orexin deficiency. Montpellier team have previously underlined in 15 patients with narcolepsy type 1 a normal level of Aβ42 in the CSF. The clinical expertise of the narcolepsy center suggested that the frequency of AD in old narcoleptic patients is low. The hypothesis was that patients with narcolepsy type 1 may be protected from amyloid brain lesions, hallmarks of the Alzheimer's process. The objective was to determine whether the brain amyloid load by PET-scan18 F-AV-45 measured with a semi-quantitative analysis (mean cortical SuVr) is lower in patients with narcolepsy type 1 older than 65 years-old than in cognitively normal age- and gender-matched controls.

Conditions

• Narcolepsy
• Amyloid Pathology

Interventions

Type	Name	Description
DEVICE	PET-scan18F-AV-45	The PET-scan18F-AV-45 is a PET-scan dedicated to analyze the amyloid load in the brain with the AV45 tracer by the measurement of the mean cortical SuVr
DEVICE	PET-scan18F-AV-45	PET-scan18F-AV-45 already done in another protocol MEMENTO-AMYging

Timeline

• Start date: 2016-04-07
• Primary completion: 2017-11-01
• Completion: 2017-11-01
• First posted: 2017-12-19
• Last updated: 2017-12-19

Locations

1 site across 1 country: France