Central and Systemic Inflammation in Alzheimer's Disease (IMABio3)

80 sporadic AD patients (40 at the stage of MCI, 40 at the stage of mild or moderate dementia), 15 familial forms of AD caused by APP, PSEN1 or PSEN2 mutations, 30 asymptomatic relatives to familial AD patients, 40 controls, 5 genetic forms of FTD

Inclusion criteria :

Sporadic AD patients at a prodromal stage:

• Be older than 30 years old.

• Progressive amnestic syndrome of the hippocampal type, defined by a free recall score

  ≤ 18 and a total recall score ≤ 40 on the Free and Cued Selective Recall Reminding Test (FCSRT).

• Absence of overt dementia.
• CDR (Clinical Dementia Rating Scale) = 0.5.
• No impact on activities of daily living, or only one item impaired at the first level of the Instrumental Activity of Daily Living Scale.
• Absence of general or systemic disorders that may interfere with cognition.
• Absence of brain lesions as determined by MRI that may account for part of the clinical presentation.

Sporadic AD patients at a mild to moderate dementia stage:

• Be older than 30 years old.
• NINCDS-AIREN criteria.
• CDR (Clinical Dementia Rating Scale) = 1 or 2

Normal controls :

• Be older than 30 years old.
• An absence of psychiatric disorder
• An absence of subjective problems with memory and normal scores on the Mini Mental State Examination (MMSE ≥ 27)

Familial symptomatic AD patients with PSEN1, PSEN2 or APP mutations:

• Be older than 18 years old.
• Patients will be identified by the team of neurogeneticists

Relatives at 50% risk of familial AD:

• These subjects will be recruited from families affected with autosomal dominant AD that is due to the mutation of the PSEN1, PSEN2 or APP genes. In these families, the first-degree relatives of patients with a mutation have a 50% risk of having the mutation that was identified in the family.

Familial frontotemporal dementia (FTD) patients :

• FTD patients with mutations in the progranulin gene or MAPT (tau) gene will be identified by the team of neurogeneticists at Rouen and Paris (Salpetriere). Familial FTD patients with known pathologies will be included regardless of the severity of the disease, given the small number of patients involved.

Concomitant therapy :

• All subjects will be asked about their history of benzodiazepine treatment: flunitrazepam, triazolam, and diazepam, which have a moderate affinity for PBR, will be forbidden or will be stopped before inclusion. Clonazepam, lorazepam, zolpidem, and zopiclone, which have a very low affinity for PBR, will be allowed. For all other benzodiazepines, specific research on their affinity toward PBR will be performed before definitive inclusion.

Subjects taking acetylcholinesterase inhibitor or memantine will be admitted.

Exclusion criteria :

• Psychiatric disorder or major depression
• Contraindication for MRI examination : carrying a cardiac pacemaker, any ferromagnetic metallic implants or foreign bodies (an internal electrical or magnetic device, a valvular prosthesis), claustrophobic subject
• Alcoholism
• Vascular lesions on MRI
• Allergy either to PiB or to DPA
• Non health insurance affiliation
• Pregnant women