Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

Andrea Vergallo; René-Sosata Bun; Nicola Toschi; Filippo Baldacci; Henrik Zetterberg; Kaj Blennow; Enrica Cavedo; Foudil Lamari; Marie-Odile Habert; Bruno Dubois; Roberto Floris; Francesco Garaci; Simone Lista; Harald Hampel; INSIGHT-preAD study group; Alzheimer Precision Medicine Initiative (APMI)

doi:10.1016/j.jalz.2018.06.3053

Association of cerebrospinal fluid α-synuclein with total and phospho-tau₁₈₁ protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

Alzheimers Dement. 2018 Dec;14(12):1623-1631. doi: 10.1016/j.jalz.2018.06.3053. Epub 2018 Jul 26.

Authors

Collaborators

C Audrain, A Auffret, H Bakardjian, F Baldacci, B Batrancourt, I Benakki, H Benali, H Bertin, A Bertrand, L Boukadida, F Cacciamani, V Causse, E Cavedo, S Cherif Touil, P A Chiesa, O Colliot, G Dalla Barba, M Depaulis, A Dos Santos, B Dubois, M Dubois, S Epelbaum, B Fontaine, H Francisque, G Gagliardi, A Genin, R Genthon, P Glasman, F Gombert, M O Habert, H Hampel, H Hewa, M Houot, N Jungalee, A Kas, M Kilani, V La Corte, F Le Roy, S Lehericy, C Letondor, M Levy, S Lista, M Lowrey, J Ly, O Makiese, I Masetti, A Mendes, C Metzinger, A Michon, F Mochel, R Nait Arab, F Nyasse, C Perrin, F Poirier, C Poisson, M C Potier, S Ratovohery, M Revillon, K Rojkova, K Santos-Andrade, R Schindler, M C Servera, L Seux, V Simon, D Skovronsky, M Thiebaut, O Uspenskaya, M Vlaincu, L F Aguilar, C Babiloni, F Baldacci, N Benda, K L Black, A L W Bokde, U Bonuccelli, K Broich, R S Bun, F Cacciola, J Castrillo, E Cavedo, R Ceravolo, P A Chiesa, O Colliot, C M Coman, J C Corvol, A C Cuello, J L Cummings, H Depypere, B Dubois, A Duggento, S Durrleman, V Escott-Price, H Federoff, M T Ferretti, M Fiandaca, R A Frank, F Garaci, R Genthon, N George, F S Giorgi, M Graziani, M Haberkamp, M O Habert, H Hampel, K Herholz, E Karran, S H Kim, Y Koronyo, M Koronyo-Hamaoui, F Lamari, T Langevin, S Lehéricy, S Lista, J Lorenceau, M Mapstone, C Neri, R Nisticò, F Nyasse-Messene, S E O'Bryant, G Perry, C Ritchie, K Rojkova, S Rossi, E Santarnecchi, L S Schneider, O Sporns, N Toschi, S R Verdooner, A Vergallo, N Villain, L Welikovitch, J Woodcock, E Younesi

Affiliations

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: [email protected].
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.

PMID: 30055132
DOI: 10.1016/j.jalz.2018.06.3053

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.

Keywords: Alzheimer's disease; Amyloid PET; Cerebrospinal fluid; Monocentric; Preclinical; SUVR; Subjective memory complainers; Synergistic; Tau protein; α-Synuclein.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / diagnosis
Amyloid / metabolism*
Apolipoprotein E4 / genetics
Biomarkers / cerebrospinal fluid
Brain / diagnostic imaging*
Brain / metabolism*
Cognition
Cohort Studies
Cross-Sectional Studies
Diagnostic Self Evaluation
Female
Humans
Male
Memory Disorders / diagnosis*
Positron-Emission Tomography
Prodromal Symptoms
alpha-Synuclein / cerebrospinal fluid*
tau Proteins / cerebrospinal fluid*

Substances

Amyloid
Apolipoprotein E4
Biomarkers
MAPT protein, human
SNCA protein, human
alpha-Synuclein
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding