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  • Levin, JohannesGerman Center for Neurodegenerative Diseases (DZNE), Bonn,Munich Cluster for Systems Neurology,University Hospital Munich (author)

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

  • Article/chapterEnglish2024

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  • 2024

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  • LIBRIS-ID:oai:lup.lub.lu.se:e5650208-9c96-45e7-a54e-1a3acec898e0
  • https://lup.lub.lu.se/record/e5650208-9c96-45e7-a54e-1a3acec898e0URI
  • https://doi.org/10.1002/alz.13818DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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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.

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  • Baiardi, Simone (author)
  • Quadalti, Corinne (author)
  • Rossi, Marcello (author)
  • Mammana, Angela (author)
  • Vöglein, JonathanGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich (author)
  • Bernhardt, AlexanderUniversity Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Perrin, Richard J.Washington University in St. Louis (author)
  • Jucker, MathiasGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University of Tübingen (author)
  • Preische, OliverUniversity of Tübingen,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Hofmann, AnnaUniversity of Tübingen,German Center for Neurodegenerative Diseases (DZNE), Bonn (author)
  • Höglinger, Günter U.German Center for Neurodegenerative Diseases (DZNE), Bonn,Munich Cluster for Systems Neurology,University Hospital Munich (author)
  • Cairns, Nigel J.University of Exeter (author)
  • Franklin, Erin E.Washington University in St. Louis (author)
  • Chrem, PatricioFundacion Para La Lucha Contra Las Enfermedades Neurologicas de La Infancia (FLENI) (author)
  • Cruchaga, CarlosWashington University in St. Louis (author)
  • Berman, Sarah B.University of Pittsburgh (author)
  • Chhatwal, Jasmeer P.Harvard Medical School (author)
  • Daniels, AlishaWashington University in St. Louis (author)
  • Day, Gregory S.Mayo Clinic Florida (author)
  • Ryan, Natalie S.University College London (author)
  • Goate, Alison M.Icahn School of Medicine at Mount Sinai (author)
  • Gordon, Brian A.Washington University in St. Louis (author)
  • Huey, Edward D.Brown University (author)
  • Ibanez, LauraWashington University in St. Louis (author)
  • Karch, Celeste M.Washington University in St. Louis (author)
  • Lee, Jae Hong (author)
  • Llibre-Guerra, JorgeWashington University in St. Louis (author)
  • Lopera, Francisco (author)
  • Masters, Colin L.University of Melbourne (author)
  • Morris, John C.Washington University in St. Louis (author)
  • Noble, James M.Columbia University (author)
  • Renton, Alan E.Icahn School of Medicine at Mount Sinai (author)
  • Roh, Jee Hoon (author)
  • Frosch, Matthew P.Massachusetts General Hospital (author)
  • Keene, C. DirkUniversity of Washington (author)
  • McLean, CatrionaAlfred Health (author)
  • Sanchez-Valle, RaquelHospital Clínic of Barcelona (author)
  • Schofield, Peter R.University of New South Wales,Neuroscience Research Australia (NeuRA) (author)
  • Supnet-Bell, CharleneWashington University in St. Louis (author)
  • Xiong, ChengjieWashington University in St. Louis (author)
  • Giese, Armin (author)
  • Hansson, OskarLund 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(Swepub:lu)mphy-ohn (author)
  • Bateman, Randall J.Washington University in St. Louis (author)
  • McDade, EricWashington University in St. Louis (author)
  • Parchi, Piero (author)
  • German Center for Neurodegenerative Diseases (DZNE), BonnMunich Cluster for Systems Neurology (creator_code:org_t)
  • Dominantly Inherited Alzheimer Network

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  • In:Alzheimer's and Dementia1552-5260

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