% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Levin:270311, author = {Levin, Johannes and Baiardi, Simone and Quadalti, Corinne and Rossi, Marcello and Mammana, Angela and Vöglein, Jonathan and Bernhardt, Alexander and Perrin, Richard J and Jucker, Mathias and Preische, Oliver and Hofmann, Anna and Höglinger, Günter U and Cairns, Nigel J and Franklin, Erin E and Chrem, Patricio and Cruchaga, Carlos and Berman, Sarah B and Chhatwal, Jasmeer P and Daniels, Alisha and Day, Gregory S and Ryan, Natalie S and Goate, Alison M and Gordon, Brian A and Huey, Edward D and Ibanez, Laura and Karch, Celeste M and Lee, Jae-Hong and Llibre-Guerra, Jorge and Lopera, Francisco and Masters, Colin L and Morris, John C and Noble, James M and Renton, Alan E and Roh, Jee Hoon and Frosch, Matthew P and Keene, C Dirk and McLean, Catriona and Sanchez-Valle, Raquel and Schofield, Peter R and Supnet-Bell, Charlene and Xiong, Chengjie and Giese, Armin and Hansson, Oskar and Bateman, Randall J and McDade, Eric and Parchi, Piero}, collaboration = {Network, Dominantly Inherited Alzheimer}, title = {α-{S}ynuclein seed amplification assay detects {L}ewy body co-pathology in autosomal dominant {A}lzheimer's disease late in the disease course and dependent on {L}ewy pathology burden.}, journal = {Alzheimer's and dementia}, volume = {20}, number = {6}, issn = {1552-5260}, address = {Hoboken, NJ}, publisher = {Wiley}, reportid = {DZNE-2024-00783}, pages = {4351 - 4365}, year = {2024}, abstract = {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.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.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.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.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.}, keywords = {Alzheimer Disease: diagnosis / Humans / Alzheimer Disease: genetics / Alzheimer Disease: pathology / Alzheimer Disease: cerebrospinal fluid / alpha-Synuclein: cerebrospinal fluid / alpha-Synuclein: genetics / Female / Male / Middle Aged / Lewy Bodies: pathology / Aged / Mutation / Brain: pathology / Amyloid beta-Peptides: cerebrospinal fluid / Amyloid beta-Peptides: metabolism / Disease Progression / alpha‐synuclein seed amplification assay (Other) / Dominantly Inherited Alzheimer Network (Other) / Lewy body pathology (Other) / alpha‐synuclein seed amplification assay (Other) / real‐time quaking‐induced conversion (Other) / alpha-Synuclein (NLM Chemicals) / Amyloid beta-Peptides (NLM Chemicals) / real‐time quaking‐induced conversion (Other)}, cin = {Clinical Research (Munich) / AG Jucker}, ddc = {610}, cid = {I:(DE-2719)1111015 / I:(DE-2719)1210001}, pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 - Disease Mechanisms (POF4-352)}, pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352}, experiment = {EXP:(DE-2719)DIAN-20090101}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:38666355}, pmc = {pmc:PMC11180868}, doi = {10.1002/alz.13818}, url = {https://pub.dzne.de/record/270311}, }