Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Giovanni B Frisoni¹, Marina Boccardi², Frederik Barkhof³, Kaj Blennow⁴, Stefano Cappa⁵, Konstantinos Chiotis⁶, Jean-Francois Démonet⁷, Valentina Garibotto⁸, Panteleimon Giannakopoulos⁹, Anton Gietl¹⁰, Oskar Hansson¹¹, Karl Herholz¹², Clifford R Jack Jr¹³, Flavio Nobili¹⁴, Agneta Nordberg¹⁵, Heather M Snyder¹⁶, Mara Ten Kate¹⁷, Andrea Varrone¹⁸, Emiliano Albanese⁹, Stefanie Becker¹⁹, Patrick Bossuyt²⁰, Maria C Carrillo¹⁶, Chiara Cerami²¹, Bruno Dubois²², Valentina Gallo²³, Ezio Giacobini²⁴, Gabriel Gold²⁵, Samia Hurst²⁶, Anders Lönneborg²⁷, Karl-Olof Lovblad²⁸, Niklas Mattsson²⁹, José-Luis Molinuevo³⁰, Andreas U Monsch³¹, Urs Mosimann³², Alessandro Padovani³³, Agnese Picco³⁴, Corinna Porteri³⁵, Osman Ratib³⁶, Laure Saint-Aubert⁶, Charles Scerri³⁷, Philip Scheltens¹⁷, Jonathan M Schott³⁸, Ida Sonni³⁹, Stefan Teipel⁴⁰, Paolo Vineis⁴¹, Pieter Jelle Visser⁴², Yutaka Yasui⁴³, Bengt Winblad⁴⁴

Affiliations

¹ Laboratory of Neuroimaging of Aging (LANVIE), University Hospitals and University of Geneva, Geneva, Switzerland; Department of Internal Medicine, University Hospitals and University of Geneva, Geneva, Switzerland. Electronic address: Giovanni.Frisoni@unige.ch.
² Laboratory of Neuroimaging of Aging (LANVIE), University Hospitals and University of Geneva, Geneva, Switzerland; Laboratory of Alzheimer Neuroimaging and Epidemiology (LANE), IRCCS S Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
³ Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, Netherlands; Institute of Neurology, University College London, London, UK; Institute of Healthcare Engineering, University College London, London, UK; European Society of Neuroradiology, Zurich, Switzerland.
⁴ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; International Federation of Clinical Chemistry and Laboratory Medicine Working Group for CSF proteins (IFCC WG-CSF), Gothenburg, Sweden.
⁵ Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, Netherlands; Istituto Universitario di Studi Superiori di Pavia, Pavia, Italy, on behalf of Federation of European Neuropsychological Societies.
⁶ Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
⁷ Leenards Memory Centre, Department of Clinical Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁸ Nuclear Medicine and Molecular Imaging Division, University Hospitals and University of Geneva, Geneva, Switzerland.
⁹ Department of Psychiatry, University Hospitals and University of Geneva, Geneva, Switzerland.
¹⁰ Institute for Regenerative Medicine-IREM, University of Zurich Campus Schlieren, Zurich, Switzerland.
¹¹ Memory Clinic, Skåne University Hospital, Lund, Sweden; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
¹² Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK.
¹³ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
¹⁴ Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy; IRCCS AOU San Martino-IST, Genoa, Italy, on behalf of the European Association of Nuclear Medicine.
¹⁵ Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
¹⁶ Alzheimer's Association, Chicago, IL, USA.
¹⁷ Department of Neurology, Alzheimer Centre, VU University Medical Centre, Amsterdam, Netherlands.
¹⁸ Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
¹⁹ Alzheimer's Switzerland, Yverdon-les-Bains, Switzerland.
²⁰ Clinical Epidemiology, University of Amsterdam, Amsterdam, Netherlands, on behalf of the European Federation of Laboratory Medicine.
²¹ Clinical Neuroscience Department, Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
²² Institut de la Mémoire et de la Maladie d'Alzheimer, Hôpital Pitié Salpêtrière, UPMC University Paris 6, Paris, France.
²³ Centre for Primary Care and Public Health, Barts and The London School of Medicine, Blizard Institute, Queen Mary University of London, London, UK.
²⁴ Department of Internal Medicine, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁵ Service of Geriatrics, Department of Internal Medicine Rehabilitation and Geriatrics, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁶ Institute for Ethics, History, and the Humanities, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁷ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
²⁸ Diagnostic and Interventional Neuroradiology, University Hospital of Geneva, Geneva, Switzerland.
²⁹ Memory Clinic, Skåne University Hospital, Lund, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
³⁰ Barcelona Beta Brain Research Centre, Pasqual Maragall Foundation, Barcelona, Spain.
³¹ Memory Clinic, University Centre for Medicine of Ageing, Felix Platter Hospital, Basel, Switzerland.
³² Department of Old Age Psychiatry, University of Bern, Bern, Switzerland.
³³ Department of Clinical Neurosciences, Faculty of Medicine, University of Brescia, Brescia, Italy.
³⁴ Laboratory of Neuroimaging of Aging (LANVIE), University Hospitals and University of Geneva, Geneva, Switzerland; Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy.
³⁵ Bioethics Unit, IRCCS S Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
³⁶ Department of Radiology, University Hospital of Geneva, Geneva, Switzerland; Division of Nuclear Medicine, University Hospital of Geneva, Geneva, Switzerland.
³⁷ Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Alzheimer Europe, Luxembourg, Luxembourg.
³⁸ Institute of Neurology, University College London, London, UK.
³⁹ PET Centre, Department of Clinical Neurosciences, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden; Division of Nuclear Medicine and Molecular Imaging, Stanford University, Standford, CA, USA.
⁴⁰ German Center for Neurodegenerative Diseases (DZNE)-Rostock/Greifswald, Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
⁴¹ Faculty of Medicine, Imperial College London, London, UK.
⁴² Department of Neurology, Alzheimer Centre, VU University Medical Centre, Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
⁴³ St Jude Children's Research Hospital, Memphis, TN, USA.
⁴⁴ Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Neurobiology, Care Siences and Society, Centre for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Huddinge, Sweden; European Alzheimer's Disease Consortium.

PMID: 28721928
DOI: 10.1016/S1474-4422(17)30159-X

Review

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

Giovanni B Frisoni et al. Lancet Neurol. 2017 Aug.

. 2017 Aug;16(8):661-676.

doi: 10.1016/S1474-4422(17)30159-X. Epub 2017 Jul 11.

Authors

Affiliations

¹ Laboratory of Neuroimaging of Aging (LANVIE), University Hospitals and University of Geneva, Geneva, Switzerland; Department of Internal Medicine, University Hospitals and University of Geneva, Geneva, Switzerland. Electronic address: Giovanni.Frisoni@unige.ch.
² Laboratory of Neuroimaging of Aging (LANVIE), University Hospitals and University of Geneva, Geneva, Switzerland; Laboratory of Alzheimer Neuroimaging and Epidemiology (LANE), IRCCS S Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
³ Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, Netherlands; Institute of Neurology, University College London, London, UK; Institute of Healthcare Engineering, University College London, London, UK; European Society of Neuroradiology, Zurich, Switzerland.
⁴ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; International Federation of Clinical Chemistry and Laboratory Medicine Working Group for CSF proteins (IFCC WG-CSF), Gothenburg, Sweden.
⁵ Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, Netherlands; Istituto Universitario di Studi Superiori di Pavia, Pavia, Italy, on behalf of Federation of European Neuropsychological Societies.
⁶ Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
⁷ Leenards Memory Centre, Department of Clinical Neuroscience, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁸ Nuclear Medicine and Molecular Imaging Division, University Hospitals and University of Geneva, Geneva, Switzerland.
⁹ Department of Psychiatry, University Hospitals and University of Geneva, Geneva, Switzerland.
¹⁰ Institute for Regenerative Medicine-IREM, University of Zurich Campus Schlieren, Zurich, Switzerland.
¹¹ Memory Clinic, Skåne University Hospital, Lund, Sweden; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
¹² Division of Neuroscience and Experimental Psychology, University of Manchester, Manchester, UK.
¹³ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
¹⁴ Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy; IRCCS AOU San Martino-IST, Genoa, Italy, on behalf of the European Association of Nuclear Medicine.
¹⁵ Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
¹⁶ Alzheimer's Association, Chicago, IL, USA.
¹⁷ Department of Neurology, Alzheimer Centre, VU University Medical Centre, Amsterdam, Netherlands.
¹⁸ Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
¹⁹ Alzheimer's Switzerland, Yverdon-les-Bains, Switzerland.
²⁰ Clinical Epidemiology, University of Amsterdam, Amsterdam, Netherlands, on behalf of the European Federation of Laboratory Medicine.
²¹ Clinical Neuroscience Department, Vita-Salute San Raffaele University, Milan, Italy; Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
²² Institut de la Mémoire et de la Maladie d'Alzheimer, Hôpital Pitié Salpêtrière, UPMC University Paris 6, Paris, France.
²³ Centre for Primary Care and Public Health, Barts and The London School of Medicine, Blizard Institute, Queen Mary University of London, London, UK.
²⁴ Department of Internal Medicine, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁵ Service of Geriatrics, Department of Internal Medicine Rehabilitation and Geriatrics, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁶ Institute for Ethics, History, and the Humanities, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁷ Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
²⁸ Diagnostic and Interventional Neuroradiology, University Hospital of Geneva, Geneva, Switzerland.
²⁹ Memory Clinic, Skåne University Hospital, Lund, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
³⁰ Barcelona Beta Brain Research Centre, Pasqual Maragall Foundation, Barcelona, Spain.
³¹ Memory Clinic, University Centre for Medicine of Ageing, Felix Platter Hospital, Basel, Switzerland.
³² Department of Old Age Psychiatry, University of Bern, Bern, Switzerland.
³³ Department of Clinical Neurosciences, Faculty of Medicine, University of Brescia, Brescia, Italy.
³⁴ Laboratory of Neuroimaging of Aging (LANVIE), University Hospitals and University of Geneva, Geneva, Switzerland; Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy.
³⁵ Bioethics Unit, IRCCS S Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
³⁶ Department of Radiology, University Hospital of Geneva, Geneva, Switzerland; Division of Nuclear Medicine, University Hospital of Geneva, Geneva, Switzerland.
³⁷ Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Alzheimer Europe, Luxembourg, Luxembourg.
³⁸ Institute of Neurology, University College London, London, UK.
³⁹ PET Centre, Department of Clinical Neurosciences, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden; Division of Nuclear Medicine and Molecular Imaging, Stanford University, Standford, CA, USA.
⁴⁰ German Center for Neurodegenerative Diseases (DZNE)-Rostock/Greifswald, Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
⁴¹ Faculty of Medicine, Imperial College London, London, UK.
⁴² Department of Neurology, Alzheimer Centre, VU University Medical Centre, Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
⁴³ St Jude Children's Research Hospital, Memphis, TN, USA.
⁴⁴ Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Neurobiology, Care Siences and Society, Centre for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Huddinge, Sweden; European Alzheimer's Disease Consortium.

PMID: 28721928
DOI: 10.1016/S1474-4422(17)30159-X

Abstract

The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.

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Comment in

Diagnostic biomarkers for Alzheimer's disease: a regulatory view.
Isaac MT, Vamvakas S, Isaac MB. Isaac MT, et al. Lancet Neurol. 2017 Aug;16(8):580-581. doi: 10.1016/S1474-4422(17)30223-5. Epub 2017 Jul 11. Lancet Neurol. 2017. PMID: 28721916 No abstract available.
Genomic profiling and diagnostic biomarkers in Alzheimer's disease.
Escott-Price V, Jones L. Escott-Price V, et al. Lancet Neurol. 2017 Aug;16(8):582-583. doi: 10.1016/S1474-4422(17)30202-8. Epub 2017 Jul 11. Lancet Neurol. 2017. PMID: 28721917 No abstract available.

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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

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