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
- Authors
- Levin, Johannes; Baiardi, Simone; Quadalti, Corinne; Rossi, Marcello; Mammana, Angela; Voeglein, Jonathan; Bernhardt, Alexander; Perrin, Richard J.; Jucker, Mathias; Preische, Oliver; Hofmann, Anna; Hoeglinger, Guenter U.; Cairns, Nigel J.; Franklin, Erin E.; Chrem, Patricio; Cruchaga, Carlos; Berman, Sarah B.; Chhatwal, Jasmeer P.; Daniels, Alisha; Day, Gregory S.; Ryan, Natalie S.; Goate, Alison M.; Gordon, Brian A.; Huey, Edward D.; Ibanez, Laura; Karch, Celeste M.; Lee, Jae-Hong; Llibre-Guerra, Jorge; Lopera, Francisco; Masters, Colin L.; Morris, John C.; Noble, James M.; Renton, Alan E.; Roh, Jee Hoon; Frosch, Matthew P.; Keene, C. Dirk; Mclean, Catriona; Sanchez-Valle, Raquel; Schofield, Peter R.; Supnet-Bell, Charlene; Xiong, Chengjie; Giese, Armin; Hansson, Oskar; Bateman, Randall J.; Mcdade, Eric; Parchi, Piero
- Issue Date
- Apr-2024
- Publisher
- Elsevier BV
- Keywords
- alpha-synuclein seed amplification assay; Dominantly Inherited Alzheimer Network; Lewy body pathology; real-time quaking-induced conversion
- Citation
- Alzheimer’s & Dementia
- Indexed
- SCIE
SCOPUS
- Journal Title
- Alzheimer’s & Dementia
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/66462
- DOI
- 10.1002/alz.13818
- ISSN
- 1552-5260
1552-5279
- Abstract
- INTRODUCTIONAmyloid 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 approximate to 50% of AD and ADAD brains.METHODSUsing an alpha-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.RESULTSNo 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 alpha-synuclein seeding activity in CSF in vivo.DISCUSSIONResults suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF alpha-synuclein SAA has low sensitivity.Highlights Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded alpha-synuclein in approximate to 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect alpha-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 alpha-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.
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Collections - 1. Basic Science > Department of Physiology > 1. Journal Articles
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