Therapeutic Evaluation of Low-dose IL-2-based Immunomodulatory Approach in Patients With Early AD

Prior treatment

• Known or supposed history (\< or = 5 years) of severe alcoholism or misuse of drugs
• Patients who are likely to require corticosteroids

Other illness

• Subject with a psychiatric evolutionary and/or badly checked.
• History of auto-immune disease
• History within the past 10 years of a primary or recurrent malignant disease
• Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders (FTD, LBD, VaD, HD, PD, PSP-CBD).
• Chronic hepatic diseases as indicated by liver function tests abnormalities
• Clinically significant evidence of Active viral infection (CMV, EBV, HCV, HBV, TPHA-VDRL, HIV)
• Current or medical history of severe cardiopathy,

Lab values

• Renal dysfunction at inclusion, clearance \<30 mL/min
• Patients with White Blood Count (WBC) \< 4.000/mm3; platelets \< 100.000/mm3; hematocrit (HCT) \< 30%.
• Patients with serum bilirubin and creatinine outside normal range.

Other

• 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.
• Epileptic subjects
• Subject under guardianship or curatorship
• Subject presenting contraindications to the MRI
• Vascular, inflammatory or expansive, visible lesion in the MRI, which can interfere on the criteria of diagnosis.
• No health insurance
• Women of childbearing potential: a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• Abnormal thyroid function
• Therapeutic trial within 1 year preceding the first study period, or participation in a trial with active or passive immunization against amyloid if patient was assigned to the active treatment arm.
• \- Severe dysfunction in a vital organ
• Patients with organ allografts.

• Patients aged \> 18
• Age of disease onset \< 70 years
• Clinical and biological diagnosis of AD based on
  • Progressive amnestic syndrome associated or not with other cognitive impairments
  • Biological criteria: CSF biomarkers suggestive of AD.
• Brain MRI congruent with the diagnosis, left to the appreciation of the investigator
• CDR (Clinical Dementia Rating Scale) = 0.5 or 1
• If patients have an antidepressant or acetylcholinesterase inhibitors treatment, patients must be treated with stable doses of treatment for at least 1 month before inclusion.
• Have a caregiver who provides a separate written informed consent to participate. If a caregiver/study informant cannot continue, one replacement is allowed.
• Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator.
• Have given written informed consent approved by the ethical review board (ERB) governing the site.
• The patient has to have a French social security number and be fluent and literate in French.