Impact of Microglial Activation on Synaptic Density in Alzheimer's Disease

Summary

This study aims to analyse, in vivo, the interplay between microglial activation and tau pathology in Alzheimer's disease (AD) using \[18F\]-DPA-714 and \[18F\]-Ro948 tracers by Position Emission Tomography (PET), and their consequences on synaptic density using \[11C\]-UCB-J, a recent PET radioligand. By coupling advanced neuroimaging techniques in AD patients, while comparing them to controls, we will be able to study, for the first time in humans, the interaction between neuroinflammation, tau pathology, synaptic density, and their impact on AD progression. Joint analyses of peripheral immune biomarkers, carried out as a secondary objective, will further aim at defining peripheral correlates of this interplay. Overall, we aim to refine AD subgroup classification in order to improve and to refine the design of new therapeutic trials.

Eligibility

Inclusion Criteria:

General Inclusion Criteria:

* Adult (older than 18 years)
* Women old enough to procreate under effective contraception
* Signed consent
* Absence of general or systemic disorders that may interfere with cognition.

Inclusion criteria for EOAD and LOAD patients:

* Progressive amnestic syndrome, associated or not with other cognitive impairments,
* CDR = 0.5 or 1
* Absence of general or systemic disorders that may interfere with cognition or PET imaging analysis,
* Absence of brain lesions as determined by MRI carried out within the framework of usual care.
* Presence of CSF biomarkers profile suggestive of AD

Inclusion criteria for controls:

* absence of subjective problems with memory and normal scores on the MMSE (MMSE \> 27) with no more than one word missing.
* older than 50 years old.
* Scores on the Free and Cued Selective Reminding Test (FCSRT) of \>25 for free recall and \>44 for total recall.
* absence of general or systemic disorders that may interfere with cognition at follow-up.

Controls will be matched to AD patients for age and education level.

Exclusion Criteria:

* Subject with a psychiatric evolutionary and/or poorly checked pathology (left to the judgement of the investigator).
* Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
* Current auto-immune disease
* Subject presenting contraindications to the 3T MRI
* Known or supposed histories (≤5 years) of severe alcoholism or misuse of drugs
* Vascular, inflammatory or expansive, visible lesion in the MRI which can interfere on the criteria of diagnosis.
* No health insurance
* Pregnant, breast-feeding woman or planning a pregnancy in two years of follow-up.
* Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders.
* Person placed under the protection of justice
* Patient under guardianship or curatorship

Conditions2

Browse More Trials