부산대학교 도서관

Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity of Alzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and breakthroughs in molecular imaging have opened up the possibility of in vivo staging of AD. Focusing on the key principles of disease staging shared across several areas of medicine, this Review highlights the potential for in vivo staging of AD to transform our understanding of preclinical AD, refine enrolment criteria for trials of disease-modifying therapies and aid clinical decision-making in the era of anti-amyloid therapeutics. We provide a state-of-the-art review of recent biomarker-based AD staging systems and highlight their contributions to the understanding of the natural history of AD. Furthermore, we outline hypothetical frameworks to stage AD severity using more accessible fluid biomarkers. In addition, by applying amyloid PET-based staging to recently published anti-amyloid therapeutic trials, we highlight how biomarker-based disease staging frameworks could illustrate the numerous pathological changes that have already taken place in individuals with mildly symptomatic AD. Finally, we discuss challenges related to the validation and standardization of disease staging and provide a forward-looking perspective on potential clinical applications.
Recent clinical trials have highlighted the need for Alzheimer disease (AD) staging rather than simply noting the presence or absence of AD pathology. This article reviews current biomarker-based AD staging systems and outlines hypothetical frameworks to stage AD severity using fluid biomarkers.
Key points: Disease staging systems are used across medicine to measure disease severity, estimate patient prognosis, determine eligibility for clinical trials and guide clinical care.Staging systems provide a model of the natural history of a disease as well as a framework to validate new biomarkers and test new interventions.Alzheimer disease (AD) has a long preclinical phase in which multiple biological changes are observable in the absence of symptoms; biomarker-based staging systems are well suited to detect and monitor these changes over the natural history of AD.Biomarker-based staging using the topography of PET ligand uptake provides information about AD severity and aids prediction of clinical outcomes.Recent work has highlighted the potential of fluid biomarker panels for the staging of AD and the development of plasma biomarker panels will substantially increase the accessibility of biomarker-based AD staging.Biomarker-based AD staging might help to guide clinical decision-making; for example, evidence suggests that individuals with lower levels of tau tracer uptake on PET respond better to anti-amyloid monoclonal antibody therapy.