Clinical validity of increased cortical uptake of amyloid ligands on PET as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework

• Published in: Neurobiology of aging Vol. 52; pp. 214 - 227
• Main Authors: Chiotis, Konstantinos, Saint-Aubert, Laure, Boccardi, Marina, Gietl, Anton, Picco, Agnese, Varrone, Andrea, Garibotto, Valentina, Herholz, Karl, Nobili, Flavio, Nordberg, Agneta, Frisoni, Giovanni B., Winblad, Bengt, Jack, Clifford R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2017
• Subjects: 5-Phases; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid; Biomarker; Biomarker-based diagnosis; Biomarkers; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Clinical validity; Development; Early diagnosis; Humans; Internal Medicine; Ligands; Neuroimaging; Neurology; Positron emission tomography; Reproducibility of Results; Neuroimaging; 5-Phases; Biomarker; Early diagnosis; Development; Amyloid; Clinical validity; Alzheimer's disease; Positron emission tomography; Biomarker-based diagnosis
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2016.07.012

The use of biomarkers has been proposed for diagnosing Alzheimer's disease in recent criteria, but some biomarkers have not been sufficiently investigated to justify their routine clinical use. Here, we evaluate in a literature review the clinical validity of amyloid positron emission tomography (PET) imaging using a structured framework developed for the assessment of oncological biomarkers. Homogenous criteria have been addressed in reviews of other Alzheimer's disease biomarkers. There is adequate evidence that the main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved. The aims of phase 3 (early detection ability) have been partly achieved, while phase 4 studies (performance in representative mild cognitive impairment patients) are currently ongoing. Phase 5 studies (quantification of impact and costs) are still to come. This review highlights the priorities to be pursued to enable the proper use of amyloid PET imaging in a clinical setting. Future investigations will primarily be large, phase 4 studies that will assess the utility of amyloid PET imaging in routine clinical practice. [Display omitted]