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.
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.
Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Department of NVS, Karolinska Institutet, Stockholm, Sweden.
Konstantinos
K
Chiotis
Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Department of NVS, Karolinska Institutet, Stockholm, Sweden.
Laure
L
Saint-Aubert
Laboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; LANVIE (Laboratory of Neuroimaging of Aging) - Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Marina
M
Boccardi
Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
Anton
A
Gietl
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Agnese
A
Picco
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Andrea
A
Varrone
Department of Neurology, Geneva University Hospitals, Geneva, Switzerland.
Valentina
V
Garibotto
The University of Manchester, Institute of Brain, Behaviour and Mental Health, Wolfson Molecular Imaging Centre, Manchester, UK.
Karl
K
Herholz
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Flavio
F
Nobili
Center for Alzheimer Research, Division of Translational Alzheimer Neurobiology, Department of NVS, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: Agneta.K.Nordberg@ki.se.
Agneta
A
Nordberg
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D000682:Amyloid; D015415:Biomarkers; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography; D015203:Reproducibility of Results
D000682:Amyloid; D015415:Biomarkers; D008024:Ligands
5-Phases; Alzheimer's disease; Amyloid; Biomarker; Biomarker-based diagnosis; Clinical validity; Development; Early diagnosis; Neuroimaging; Positron emission tomography