Andrea Vergallo1, René-Sosata Bun2, Nicola Toschi3, Filippo Baldacci4, Henrik Zetterberg5, Kaj Blennow6, Enrica Cavedo7, Foudil Lamari8, Marie-Odile Habert9, Bruno Dubois10, Roberto Floris11, Francesco Garaci12, Simone Lista2, Harald Hampel2. 1. AXA Research Fund & Sorbonne University Chair, Paris, France; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. Electronic address: andrea.vergallo@icm-institute.org. 2. AXA Research Fund & Sorbonne University Chair, Paris, France; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. 3. Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy; Department of Radiology, "Athinoula A. Martinos" Center for Biomedical Imaging, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 4. AXA Research Fund & Sorbonne University Chair, Paris, France; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 5. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute, London, UK. 6. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 7. AXA Research Fund & Sorbonne University Chair, Paris, France; Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France; Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. 8. AP-HP, UF Biochimie des Maladies Neuro-métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 9. Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France; Centre pour l'Acquisition et le Traitement des Images (www.cati-neuroimaging.com), France; AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Nucléaire, Paris, France. 10. Sorbonne University, GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. 11. Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy. 12. Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy; Casa di Cura "San Raffaele Cassino", Cassino, Italy.
Abstract
INTRODUCTION: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. METHODS: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). RESULTS: We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. DISCUSSION: Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
INTRODUCTION: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. METHODS: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). RESULTS: We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. DISCUSSION: Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.
Authors: Daniel Twohig; Elena Rodriguez-Vieitez; Sigrid B Sando; Guro Berge; Camilla Lauridsen; Ina Møller; Gøril R Grøntvedt; Geir Bråthen; Kalicharan Patra; Guojun Bu; Tammie L S Benzinger; Celeste M Karch; Anne Fagan; John C Morris; Randall J Bateman; Agneta Nordberg; Linda R White; Henrietta M Nielsen Journal: Acta Neuropathol Commun Date: 2018-11-26 Impact factor: 7.578
Authors: Davide Bruno; Chelsea Reichert Plaska; Daniel P A Clark; Henrik Zetterberg; Kaj Blennow; Marcel M Verbeek; Nunzio Pomara Journal: Int J Neurosci Date: 2020-03-31 Impact factor: 2.292