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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

Levin, Johannes (author)
Munich Cluster for Systems Neurology,German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
Baiardi, Simone (author)
Quadalti, Corinne (author)
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Rossi, Marcello (author)
Mammana, Angela (author)
Vöglein, Jonathan (author)
University Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn
Bernhardt, Alexander (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
Perrin, Richard J. (author)
Washington University in St. Louis
Jucker, Mathias (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Tübingen
Preische, Oliver (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Tübingen
Hofmann, Anna (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Tübingen
Höglinger, Günter U. (author)
Munich Cluster for Systems Neurology,German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
Cairns, Nigel J. (author)
University of Exeter
Franklin, Erin E. (author)
Washington University in St. Louis
Chrem, Patricio (author)
Fundacion Para La Lucha Contra Las Enfermedades Neurologicas de La Infancia (FLENI)
Cruchaga, Carlos (author)
Washington University in St. Louis
Berman, Sarah B. (author)
University of Pittsburgh
Chhatwal, Jasmeer P. (author)
Harvard Medical School
Daniels, Alisha (author)
Washington University in St. Louis
Day, Gregory S. (author)
Mayo Clinic Florida
Ryan, Natalie S. (author)
University College London
Goate, Alison M. (author)
Icahn School of Medicine at Mount Sinai
Gordon, Brian A. (author)
Washington University in St. Louis
Huey, Edward D. (author)
Brown University
Ibanez, Laura (author)
Washington University in St. Louis
Karch, Celeste M. (author)
Washington University in St. Louis
Lee, Jae Hong (author)
Llibre-Guerra, Jorge (author)
Washington University in St. Louis
Lopera, Francisco (author)
Masters, Colin L. (author)
University of Melbourne
Morris, John C. (author)
Washington University in St. Louis
Noble, James M. (author)
Columbia University
Renton, Alan E. (author)
Icahn School of Medicine at Mount Sinai
Roh, Jee Hoon (author)
Frosch, Matthew P. (author)
Massachusetts General Hospital
Keene, C. Dirk (author)
University of Washington
McLean, Catriona (author)
Alfred Health
Sanchez-Valle, Raquel (author)
Hospital Clínic of Barcelona
Schofield, Peter R. (author)
Neuroscience Research Australia (NeuRA),University of New South Wales
Supnet-Bell, Charlene (author)
Washington University in St. Louis
Xiong, Chengjie (author)
Washington University in St. Louis
Giese, Armin (author)
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
Bateman, Randall J. (author)
Washington University in St. Louis
McDade, Eric (author)
Washington University in St. Louis
Parchi, Piero (author)
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 (creator_code:org_t)
 
2024
2024
English.
In: Alzheimer's and Dementia. - 1552-5260.
Related links:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
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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