NCT07007208

Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk

Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk.

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: University Hospital, Toulouse · Academic / Other
• Sex: All
• Age: 60 Years – 100 Years
• Healthy volunteers: Accepted

Summary

Alzheimer's disease (AD) is characterized by a long-lasting silent phase. Among initial events, emergence of tau pathology in locus coeruleus (LC) brainstem nucleus, well before the one observed in medial temporal cortex, is highly relevant. LC integrity and function can be assessed in vivo with MRI and pupil measures. The current research proposes to evaluate these LC markers in an aged healthy cohort (n=100, with half APOE4 positive) and to relate these markers with cerebral tau pathology, AD risk and cognitive function.

Detailed description

Early tau pathology in the LC may induce dysfunction of the LC-NA system, contribute to initial cognitive decline and possibly be predictive of future AD occurrence. The present project has the following objectives: 1) to relate different biomarkers of LC function measured in vivo with AD risk and future AD occurrence, in order to evaluate their relevance for earliest AD diagnosis, 2) to investigate how LC biomarkers can account for underlying brain tau pathology in asymptomatic older individuals; a related objective will be to validate LC biomarkers as reliable proxies of tau pathology occurrence, and 3) to study the link between LC biomarkers and cognitive performance. To complete these objectives, the project will evaluate, in healthy older volunteers from the INSPIRE-T cohort (n=100, \> 60 years old), biomarkers of LC neuronal integrity, LC-forebrain connectivity, and LC tonic and phasic activity. Additionally, a positon emission tomography (PET) exam will be conducted using tau-specific tracer. Detailed cognitive assessment will also be performed, including assessment of a priori NA-dependent and NA-independent cognitive functions. In the studied cohort (n = 100), half volunteers will be recruited based on genetic AD risk (APOE4 positive) and the other half based on the absence of risk (APOE4 negative).

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
DRUG	a positon emission tomography (PET) exam	TEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq)
OTHER	MRI Contrast	Data acquisition will include different sequences (anatomical MRI, resting fMRI). The MRI sequences performed will be anatomical imaging (i.e. T1 imaging, FLAIR), a diffusion sequence, a neuromelanin-sensitive sequence and functional imaging at rest (i.e. "the resting state", which allows the functional connectivity within the so-called "default" network to be assessed).
OTHER	oculometry assessment	Pupillometry and oculometry will be conducted using an EyeBrain medical device (class IIa). Several cognitive tasks will be submitted to the participant, during which the same measurements will be taken. Different stimuli will be presented on the computer screen (visual scenes, text, geometric shapes) during the eye tracking measurement, and an instruction (cognitive task, such as semantic categorization, free exploration of the gaze, reading, saccade execution) will be associated with each type of stimulus. The successive stimuli will be spaced more than 7 secondes apart in order to allow the pupillary response to the first stimulus to be recorded and then to return to the basal diameter before presentation of the next stimulus.
OTHER	cognitive exams	Cognitive measures will be acquired during an evaluation session through 6 interactive cognitive exercises. These exercises are developed using tools offered by Covirtua Healthcare.

Timeline

• Start date: 2026-01-01
• Primary completion: 2029-01-31
• Completion: 2029-01-31
• First posted: 2025-06-05
• Last updated: 2025-12-16

Locations

1 site across 1 country: France