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

Toulouse University Hospital

Status and phase: Not yet enrolling; Phase 2

Conditions: Alzheimer Disease

Treatments: Other: cognitive exams; Other: oculometry assessment; Drug: a positon emission tomography (PET) exam; Other: MRI Contrast

Study type: Interventional

Funder types: Other

Identifiers

NCT07007208

2023-507668-38-00 (EU Trial (CTIS) Number)

RC31/23/0371

Details and patient eligibility

About

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.

Full 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).

Enrollment: 100 estimated patients

Sex: All

Ages: 60 to 100 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

experimental arm

Experimental group

Description:

TEP exam, MRI exam, oculometry assessment and cognitive tasks

Treatment:

Other: MRI Contrast

Drug: a positon emission tomography (PET) exam

Other: oculometry assessment

Other: cognitive exams