This project aims to establish a neuroimaging framework which informs about microscopic brain composition and apply it to study neurodegeneration in a genetic mouse model of Alzheimer’s disease (AD). AD is the most common cause of dementia, characterized by progressive neurodegenerative changes leading to a gradual cognitive loss and memory impairment. Pathological changes in AD are characterized by the accumulation of proteins to form amyloid plaques and tau-tangles as well as by variations in microscopic brain composition such as cell body density, neurite density, axon and myelin morphology, which can precede macroscopic brain atrophy and clinical symptoms even by decades. Thus, developing imaging biomarkers which can inform about these changes throughout the brain is a crucial step for early diagnosis and a better understanding of the disease. To achieve this goal, this proposal takes an interdisciplinary approach combining state-of-the-art magnetic resonance imaging (MRI) modalities and novel computational methods, and has the following objectives: 1. Develop and validate a neuroimaging framework which encompasses advanced diffusion MRI and multi-exponential T2 MRI to map microscopic brain composition (markers of soma size and density, neurite density, axon diameter and myelin fraction). Pre-clinical imaging will be performed both in-vivo and ex-vivo in wild type mice and compared with histological staining 2. Apply this methodology to investigate the changes in microscopic brain composition with the progression of AD in the APP/PS1 transgenic mouse model which develops Aβ-plaques, mimicking the early disease stages. 3. Study the association between neurodegeneration and the development of Aβ-plaques, that will be quantified based on both MR micro-imaging with ultra-high resolution and histological staining. Accomplishing these objectives will be a stepping stone for Neuroimaging of degenerative disorders, especially AD.
Project partnersFundacao D. Anna Sommer Champalimaud E Dr. Carlos Montez Champalimaud