A3D is a phase I/II clinical trial. The primary objective is to evaluate the safety of allogeneic adipose tissue derived-stem cells (AdMSC) administered by intravenous (IV) route in mild to moderate Alzheimer disease (AD) using a dose escalation protocol.

Bone narrow derived-stem cells (MSC) or adipose tissue-derived stem cells (AdMSC) are widely used in clinical research. The allogeneic approach is currently being considered in indications such as Crohn's disease and graft-versus-host disease. The potential effects of MSCs would be associated with paracrine effects via the secretion of neurotrophic cytokines capable of stimulating endogenous neurogenesis, anti-inflammatory, and immuno-modulatory factors. The recent CRATUS study consisting of IV administration of allogeneic MSCs in frail elderly participants showed a positive effect on functional performance, cognitive performance and inflammation measures. A3D is a phase I/II clinical trial whose primary objective is to evaluate the safety of allogeneic AdMSC IV administration in mild to moderate AD using a dose escalation protocol. Initially, 3 patients will receive the lowest dose (50x106 AdMSC). If the safety analysis of the first 3 patients injected by 50x106 AdMSC does not show clinically significant adverse events (AE) after 6 months of evaluation, 100x106 AdMSC administration may be started in 3 new patients. On the other hand, if the safety analysis of the first 3 patients shows a clinically significant AE related to the treatment, 3 new patients will be infused at this same dose before making a final decision on the possibility of dose escalation. Thus, the "100x106 AdMSC " group will only start after the 6-month follow-up and safety analysis completed in the "50x106 AdMSC " group.

Inclusion Criteria:

• Patient between 50 and 85 years old
• AD diagnosis according to NIA-AA 2011 criteria at a mild to moderate stage :

MMSE score between 14 and 26 (include) positive AD amyloid biomarker

• CDR (clinical dementia rating) score ≥ 1
• Patient with no absolute contraindications for PET or MRI scans
• Consent signed by the patient and study partner
• presence of primary caregiver
• Patient with social security coverage

Exclusion Criteria:

• Brain disease (other than AD) that may cause dementia
• Presence of concomitant pathologies not permitting participation in the study
• Concurrent participation in other research that may influence the testing of the A3D study
• Carrier of a pacemaker, valve prosthesis or other internal magnetic or electronic system, history of neurosurgery or aneurysm surgery, presence of metal fragments in the eyes, brain or marrow, claustrophobia
• PET scan performed in the previous year (research context)
• History of cancer diagnosed within the last 5 years
• Presence of > 4 brain microbleeds, a single area of superficial siderosis, or evidence of previous macrohaemorrhage assessed by brain MRI scan
• Regular use of corticosteroids or other steroidal anti-inflammatory drugs (e. g. prednisone)
• Presence of an autoimmune disease (e. g. rheumatoid arthritis, systemic lupus erythematosus) with the exception of psoriasis
• Pregnant or breastfeeding woman
• Adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision For patients who will participate in the optional adipose puncture (only carried out in the Toulouse center): Antithrombotic treatment and xylocaine allergy are prohibited.