How molecular imaging studies can disentangle disease mechanisms in age-related neurodegenerative disorders

The population aged over 65 is growing fast worldwide, and is predicted to reach 1.5 billion by the year 2050. In parallel, relentlessly progressive neurodegenerative diseases, including Alzheimer’s disease and other late-onset dementias, Parkinson’s disease and other movement disorders affect elderly individuals and are emerging as a major socioeconomic and healthcare challenge. Neurodegeneration is a long process preceding clinical symptomatology by decades, where aging is the most important risk factor. In search for solutions and new therapies, the attention towards neurodegenerative diseases is shifting from the description of clinical symptoms and signs to the characterization of biological alterations spanning across the disease continuum, including the preclinical stages. In vivo neuroimaging with positron emission tomography and magnetic resonance imaging have contributed remarkably to elucidating the pathogenic and pathophysiological mechanisms underpinning neurodegenerative conditions, characterizing biomarkers of neurodegeneration and facilitating the individuation of therapeutic targets and early drug development. As such, these in vivo imaging technologies carry the promise of significantly contributing to the advancement of the precision medicine model in this group of late-onset diseases. This chapter reviews the advances of in vivo molecular imaging in investigating the biological mechanisms of aging and age-related neurodegeneration, with a perspective towards the translation of state-of-the-art neuroimaging technologies to a more precise phenotypic characterization of patients, assisting in the discovery and development of novel and efficacious medicines, based on innovative clinical trials with clinically meaningful outcome measures. This ultimately improves clinical management, quality of life and a better prognosis to future sufferers of these debilitating diseases of old age.