Abstract
Diseases of the central nervous system are common often chronic conditions associated with significant morbidity. In particular, neurodegenerative disorders including Alzheimer's and Parkinson's disease constitute a major health and socio-economic challenge with increasing incidence in many industrialized countries with aging populations. Recent work has established the primary role of abnormal protein accumulation and the spread of disease-specific deposits in brain as a factor in neurotoxicity and disruption of functional networks. A range of therapeutics from small molecules to antibodies targeting these proteinopathies are now in Phase 2 and Phase 3 clinical trials. These studies are methodologically challenging owing to difficulty of accurate diagnosis in early disease, the slow and variable rates of progression between individuals, and efficacy measures which may be cofounded by the symptomatic improvements due to treatment that does not reflect disease course modification. Further, the ideal candidates for these treatments would be at-risk, or premanifest persons in whom the pathological process of the neurodegenerative disorder has begun, but who are clinically normal and extremely difficult to identify. Scintigraphic imaging with PET and SPECT in trials offers the opportunity to interrogate pathophysiologic processes like protein deposition with high specificity. This review summarizes the current implementation of these imaging biomarkers and the implications for future management of neurodegenerative disorders and CNS drug development in general.
- Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.