Neuroimaging Biomarkers in Alzheimer’s Disease and Related Disorders

Since about 2017 neuroimaging biomarkers, particularly beta-amyloid and tau imaging, have become critical to screen Alzheimer’s disease (AD) patients for clinical trials and to evaluate trial outcome. With the arrival of two monoclonal antibodies proven to reduce the amount of beta-amyloid in the brain and to have a modest therapeutic benefit on the clinical course, these biomarkers have become useful in clinical work as well as in research. Neurodegeneration in all disorders causing dementia can be measured with magnetic resonance imaging (MRI) and with the cerebral metabolic map provided by 18F-fluorodeoxyglucose positron-emission tomography (PET). An MRI technique particularly useful is measuring the thickness of the cortical ribbon and comparing it to a set of controls. Cortical thickness and metabolism are reduced mostly in post-Rolandic structures in AD, but in pre-Rolandic structures in frontotemporal dementia (FTD). Brain inflammation is an important, and until recently neglected, component of neurodegenerative disorders leading to dementia. Brain inflammation can be measured with PET tracers that bind to the translocator protein, which is expressed by microglial cells and astrocytes. Thus, the various components of dementia pathology can be measured with neuroimaging biomarkers at all stages of these diseases, from the pre-symptomatic stage to the advanced stages. Determining the stage of the disease in each patient is critical for clinical trial screening and to apply to each the correct therapeutic approach in the clinic. Therapy with clinically available monoclonal antibodies targeting beta-amyloid can cause brain edema or microhemorrhages; both these changes can be monitored with MRI.