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FältnamnIndikatorerMetadata
00006821naa a2200877 4500
001oai:lup.lub.lu.se:e5650208-9c96-45e7-a54e-1a3acec898e0
003SwePub
008240506s2024 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/e5650208-9c96-45e7-a54e-1a3acec898e02 URI
0247 a https://doi.org/10.1002/alz.138182 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Levin, Johannesu Munich Cluster for Systems Neurology,German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich4 aut
2451 0a 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
264 1c 2024
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
653 a alpha-synuclein seed amplification assay
653 a Dominantly Inherited Alzheimer Network
653 a Lewy body pathology
653 a real-time quaking-induced conversion
7001 a Baiardi, Simone4 aut
7001 a Quadalti, Corinne4 aut
7001 a Rossi, Marcello4 aut
7001 a Mammana, Angela4 aut
7001 a Vöglein, Jonathanu University Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn4 aut
7001 a Bernhardt, Alexanderu German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich4 aut
7001 a Perrin, Richard J.u Washington University in St. Louis4 aut
7001 a Jucker, Mathiasu German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Tübingen4 aut
7001 a Preische, Oliveru German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Tübingen4 aut
7001 a Hofmann, Annau German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Tübingen4 aut
7001 a Höglinger, Günter U.u Munich Cluster for Systems Neurology,German Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich4 aut
7001 a Cairns, Nigel J.u University of Exeter4 aut
7001 a Franklin, Erin E.u Washington University in St. Louis4 aut
7001 a Chrem, Patriciou Fundacion Para La Lucha Contra Las Enfermedades Neurologicas de La Infancia (FLENI)4 aut
7001 a Cruchaga, Carlosu Washington University in St. Louis4 aut
7001 a Berman, Sarah B.u University of Pittsburgh4 aut
7001 a Chhatwal, Jasmeer P.u Harvard Medical School4 aut
7001 a Daniels, Alishau Washington University in St. Louis4 aut
7001 a Day, Gregory S.u Mayo Clinic Florida4 aut
7001 a Ryan, Natalie S.u University College London4 aut
7001 a Goate, Alison M.u Icahn School of Medicine at Mount Sinai4 aut
7001 a Gordon, Brian A.u Washington University in St. Louis4 aut
7001 a Huey, Edward D.u Brown University4 aut
7001 a Ibanez, Laurau Washington University in St. Louis4 aut
7001 a Karch, Celeste M.u Washington University in St. Louis4 aut
7001 a Lee, Jae Hong4 aut
7001 a Llibre-Guerra, Jorgeu Washington University in St. Louis4 aut
7001 a Lopera, Francisco4 aut
7001 a Masters, Colin L.u University of Melbourne4 aut
7001 a Morris, John C.u Washington University in St. Louis4 aut
7001 a Noble, James M.u Columbia University4 aut
7001 a Renton, Alan E.u Icahn School of Medicine at Mount Sinai4 aut
7001 a Roh, Jee Hoon4 aut
7001 a Frosch, Matthew P.u Massachusetts General Hospital4 aut
7001 a Keene, C. Dirku University of Washington4 aut
7001 a McLean, Catrionau Alfred Health4 aut
7001 a Sanchez-Valle, Raquelu Hospital Clínic of Barcelona4 aut
7001 a Schofield, Peter R.u Neuroscience Research Australia (NeuRA),University of New South Wales4 aut
7001 a Supnet-Bell, Charleneu Washington University in St. Louis4 aut
7001 a Xiong, Chengjieu Washington University in St. Louis4 aut
7001 a Giese, Armin4 aut
7001 a Hansson, Oskaru 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 Hospital4 aut0 (Swepub:lu)mphy-ohn
7001 a Bateman, Randall J.u Washington University in St. Louis4 aut
7001 a McDade, Ericu Washington University in St. Louis4 aut
7001 a Parchi, Piero4 aut
7102 a Munich Cluster for Systems Neurologyb German Center for Neurodegenerative Diseases (DZNE), Bonn4 org
7102 a Dominantly Inherited Alzheimer Network
7730 t Alzheimer's and Dementiax 1552-5260
8564 u http://dx.doi.org/10.1002/alz.13818x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/e5650208-9c96-45e7-a54e-1a3acec898e0
8564 8u https://doi.org/10.1002/alz.13818

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