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α-Synuclein seed am...
α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
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- Levin, Johannes (author)
- Munich Cluster for Systems Neurology,German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
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Baiardi, Simone (author)
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Quadalti, Corinne (author)
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Rossi, Marcello (author)
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Mammana, Angela (author)
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- Vöglein, Jonathan (author)
- University Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Bernhardt, Alexander (author)
- University Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Perrin, Richard J. (author)
- Washington University in St. Louis
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- Jucker, Mathias (author)
- University of Tübingen,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Preische, Oliver (author)
- University of Tübingen,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Hofmann, Anna (author)
- University of Tübingen,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Höglinger, Günter U. (author)
- University Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn,Munich Cluster for Systems Neurology
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- Cairns, Nigel J. (author)
- University of Exeter
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- Franklin, Erin E. (author)
- Washington University in St. Louis
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- Chrem, Patricio (author)
- Fundacion Para La Lucha Contra Las Enfermedades Neurologicas de La Infancia (FLENI)
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- Cruchaga, Carlos (author)
- Washington University in St. Louis
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- Berman, Sarah B. (author)
- University of Pittsburgh
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- Chhatwal, Jasmeer P. (author)
- Harvard Medical School
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- Daniels, Alisha (author)
- Washington University in St. Louis
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- Day, Gregory S. (author)
- Mayo Clinic Florida
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- Ryan, Natalie S. (author)
- University College London
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- Goate, Alison M. (author)
- Icahn School of Medicine at Mount Sinai
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- Gordon, Brian A. (author)
- Washington University in St. Louis
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- Huey, Edward D. (author)
- Brown University
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- Ibanez, Laura (author)
- Washington University in St. Louis
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- Karch, Celeste M. (author)
- Washington University in St. Louis
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Lee, Jae Hong (author)
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- Llibre-Guerra, Jorge (author)
- Washington University in St. Louis
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Lopera, Francisco (author)
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- Masters, Colin L. (author)
- University of Melbourne
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- Morris, John C. (author)
- Washington University in St. Louis
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- Noble, James M. (author)
- Columbia University
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- Renton, Alan E. (author)
- Icahn School of Medicine at Mount Sinai
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Roh, Jee Hoon (author)
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- Frosch, Matthew P. (author)
- Massachusetts General Hospital
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- Keene, C. Dirk (author)
- University of Washington
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- McLean, Catriona (author)
- Alfred Health
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- Sanchez-Valle, Raquel (author)
- Hospital Clínic of Barcelona
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- Schofield, Peter R. (author)
- Neuroscience Research Australia (NeuRA),University of New South Wales
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- Supnet-Bell, Charlene (author)
- Washington University in St. Louis
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- Xiong, Chengjie (author)
- Washington University in St. Louis
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Giese, Armin (author)
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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- Bateman, Randall J. (author)
- Washington University in St. Louis
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- McDade, Eric (author)
- Washington University in St. Louis
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Parchi, Piero (author)
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(creator_code:org_t)
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- 2024
- 2024
- English 15 s.
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In: Alzheimer's and Dementia. - 1552-5260. ; 20:6, s. 4351-4365
- Related links:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- alpha-synuclein seed amplification assay
- Dominantly Inherited Alzheimer Network
- Lewy body pathology
- real-time quaking-induced conversion
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Levin, Johannes
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Baiardi, Simone
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Quadalti, Corinn ...
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Rossi, Marcello
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Mammana, Angela
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Vöglein, Jonatha ...
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show more...
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Bernhardt, Alexa ...
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Perrin, Richard ...
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Jucker, Mathias
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Preische, Oliver
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Hofmann, Anna
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Höglinger, Günte ...
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Cairns, Nigel J.
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Franklin, Erin E ...
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Chrem, Patricio
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Cruchaga, Carlos
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Berman, Sarah B.
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Chhatwal, Jasmee ...
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Daniels, Alisha
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Day, Gregory S.
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Ryan, Natalie S.
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Goate, Alison M.
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Gordon, Brian A.
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Huey, Edward D.
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Ibanez, Laura
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Karch, Celeste M ...
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Lee, Jae Hong
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Llibre-Guerra, J ...
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Lopera, Francisc ...
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Masters, Colin L ...
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Morris, John C.
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Noble, James M.
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Renton, Alan E.
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Roh, Jee Hoon
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Frosch, Matthew ...
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Keene, C. Dirk
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McLean, Catriona
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Sanchez-Valle, R ...
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Schofield, Peter ...
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Supnet-Bell, Cha ...
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Xiong, Chengjie
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Giese, Armin
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Hansson, Oskar
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Bateman, Randall ...
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McDade, Eric
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Parchi, Piero
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Alzheimer's and ...
- By the university
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Lund University