Pathological sensitivity of MRI biomarkers in Alzheimer’s disease

Neuroimaging plays an important role in Alzheimer’s disease, from diagnosis to monitoring of disease progression and treatment effects. However, it still remains unclear what the pathophysiological driving forces of neuroimaging outcomes are. This is where Amsterdam UMC and Qynapse join forces; to define the pathological sensitivity of imaging markers currently used in the Alzheimer’s disease clinical setting.

Alzheimer’s disease does not only impact the patient, but also their family and caregivers, healthcare professionals and society in general. Alzheimer’s disease comes with a variety of cognitive symptoms; from memory problems to problems with information processing, spatial orientation, language and executive functioning. Due to this heterogeneity, making a diagnosis can be difficult. Let alone give an indication on progress and prognosis.

When brain tissue from a donor with Alzheimer’s disease is assessed under a microscope, the disease characterizes itself by accumulation of Amyloid-beta and phosphorylated tau proteins. Based on this information a definite diagnosis can be made. However, this is of limited value to the patient at the neurologists’ office. We believe MRI can play a mediating role between neuropathology and the clinical setting. MRI is in continuous development to better reflect underlying pathological burden, but requires validation.

The main aim of the current project is to define the pathological sensitivity of various MRI sequences in Alzheimer’s disease, with a specific focus on differentiating typical (amnestic) and more atypical (non-amnestic) clinical presentations. We utilize a unique pipeline which combines MRIs made during life, MRIs made just after death, and neuropathological validation. We expect to identify MRI patterns sensitive to underlying pathological burden, that could help give a better understanding of the patient’s disease progress. Improvements in this area have a positive influence on patients, caretakers and society in general.