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

NCT ID: NCT07007208

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2029-01-31

Brief Summary

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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

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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

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Alzheimer Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

single group with ApoE4 carriers (n=50) and non-ApoE4 carriers (n=50)
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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experimental arm

TEP exam, MRI exam, oculometry assessment and cognitive tasks

Group Type EXPERIMENTAL

a positon emission tomography (PET) exam

Intervention Type DRUG

TEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq)

MRI Contrast

Intervention Type OTHER

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).

oculometry assessment

Intervention Type OTHER

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.

cognitive exams

Intervention Type OTHER

Cognitive measures will be acquired during an evaluation session through 6 interactive cognitive exercises. These exercises are developed using tools offered by Covirtua Healthcare.

Interventions

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a positon emission tomography (PET) exam

TEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq)

Intervention Type DRUG

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).

Intervention Type 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.

Intervention Type 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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Participant in the INSPIRE-T cohort
* Normal cognitive assessment
* MMSE score ≥ 27 out of 30 (Mini-Mental State Examination)
* Normal visual abilities (in corrected or uncorrected vision)
* Normal motor skills

Exclusion Criteria

* Subjects with a contraindication to MRI exam
* Subjects with a known allergic reaction to the PET radiopharmaceutical (\[18F\] Flortaucipir) or any of its excipients
* Subjects with an ophthalmological pathology making oculometric measurements difficult
* Subjects with neurological or psychiatric pathologies
Minimum Eligible Age

60 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University Hospital of Toulouse

Toulouse, , France

Site Status

Countries

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France

Central Contacts

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PAYOUX P Pierre, MD

Role: CONTACT

+33 (0)562746169

DELRIEU J Julien, MD

Role: CONTACT

+33 (0)5 61 77 70 58

Facility Contacts

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Payoux Pierre, MD

Role: primary

+33 (0)5 62 74 61 69

Delrieu Julien, MD

Role: backup

+33 (0)5 61 77 70 58

Other Identifiers

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2023-507668-38-00

Identifier Type: CTIS

Identifier Source: secondary_id

RC31/23/0371

Identifier Type: -

Identifier Source: org_study_id