Consortium of Neuroimmunology of Mood Disorders and Alzheimer's Disease. (360G-Wellcome-104025_Z_14_Z)

We propose to form a consortium of academic and industrial partners to address the therapeutic challenges of Alzheimers disease and mood disorders by a shared, innovative focus on immunological mechanisms of these key neuropsychiatric disorders and their treatment by anti-inflammatory drugs. The industrial partners (Janssen and Lundbeck) will contribute drug discovery know-how and access to anti-inflammatory drugs. The academic partners will contribute expertise in neuroimaging, clinical phen otyping, animal models and informatics. The work will be organised as two programmes, focused on Alzheimer's disease and mood disorders, and four cross-cutting technical platforms (cytometry, proteomics, PET and MRI). In phase 1 (years 1-3), we will validate peripheral immunological phenotypes, e.g., cytokine levels or macrophage transcriptomes, as markers of Alzheimer's disease and mood disorders. We will seek mechanistically to link peripheral immunophenotypes to markers of central (brain) inflammation and microglial activation; to brain function and behaviour; and to longitudinal changes in the clinical phenotypes and animal models. In phase 2 (years 3-5), we will use these biomarkers in experimental medicine studies designed to test mechanism-of-action and / or therapeutic proof-of-concept of anti-inflammatory drugs in immunologically stratified cohorts of patients with Alzheimer's disease or mood disorders.