ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
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.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 33 citations in OpenAlex.
- Spatial multi-omics identifies early synaptic pruning and context-specific dopaminergic vulnerability in synucleinopathies.Nature communications · 2026Article
- Deep learning-based MRI analysis reveals Lewy body co-pathology accelerates brain aging in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A Systematic Comparison of Alpha-Synuclein Seed Amplification Assays for Increasing Reproducibility.Annals of clinical and translational neurology · 2026Review
- Co-pathologies and biological processes beyond amyloid-beta and tau in people with Alzheimer's disease: Evidence from clinical cohort studies.Journal of internal medicine · 2026Review
- ATNIVS biomarker heterogeneity in real-world patients receiving lecanemab.The journal of prevention of Alzheimer's disease · 2026Article
- Amyloid-linked versus age-driven copathologies in Alzheimer's dementia: differential associations withResearch square · 2026Article
- Towards biomarker-based diagnosis of Parkinson disease.Nature reviews. Neurology · 2026Review
- From clinical phenotypes to molecular stratification: early differential diagnosis of four-repeat tauopathies.Frontiers in aging neuroscience · 2026Review
- A Biomarker-Based Classification of Corticobasal Syndrome.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Quantitative measurements of α-synuclein seeds in CSF inform diagnosis of synucleinopathies.Journal of Parkinson's disease · 2025Article
- Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Amygdala-predominant Lewy bodies associate with cognitive decline and amygdala atrophy in Alzheimer's disease neuropathological change.Journal of neurology · 2025Article
- Strain-Distinct α-Synuclein and Tau Cross-Seeding Uncovered by Correlative Approach with Optical Photothermal Infrared Sub-Micron Imaging.Journal of the American Chemical Society · 2025Article
- Two-step detection of Lewy body pathology via smell-function testing and CSF α-synuclein seed amplification.Nature communications · 2025Article
- Implications and opportunities regarding biological frameworks in overt and prodromal dementia with Lewy bodies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Alpha-synuclein co-pathology in Down syndrome-associated Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Seeding amplification assay: Limitations and insights for enhanced clinical and research applications.Journal of Parkinson's disease · 2025Review
- Alpha synuclein co-pathology is associated with accelerated amyloid-driven tau accumulation in Alzheimer's disease.Molecular neurodegeneration · 2025Article
- A quantitative Lewy-fold-specific alpha-synuclein seed amplification assay as a progression marker for Parkinson's disease.Acta neuropathologica · 2025Article
- Initial biological classification of Lewy body diseases: No consensus on terminology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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Authors and funding
47 authors at 20 institutions in 10 countries.
Johannes LevinDepartment of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.ORCID 0000-0001-5092-4306
Simone BaiardiDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Corinne QuadaltiIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Marcello RossiIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Angela MammanaIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Jonathan VögleinDepartment of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
Alexander BernhardtDepartment of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
Richard J PerrinDepartment of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Mathias JuckerGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Oliver PreischeGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Anna HofmannGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Günter U HöglingerDepartment of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
Nigel J CairnsLiving Systems Institute, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Erin E FranklinDepartment of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Patricio ChremFLENI, Montañeses 2325 (C1428AQK), Buenos Aires, Argentina.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA.
Sarah B BermanUniversity of Pittsburgh Neurology, Pittsburgh, Pennsylvania, USA.
Jasmeer P ChhatwalDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Alisha DanielsDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic in Florida, Jacksonville, Florida, USA.
Natalie S RyanDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
Alison M GoateDepartment of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Brian A GordonDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Edward D HueyButler Hospital, Brown Center for Alzheimer's Disease Research, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA.
Celeste M KarchDepartment of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri, USA.
Jae-Hong LeeDepartment of Neurology, Asan Medical Center, Seoul, South Korea.
Jorge Llibre-GuerraDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Francisco LoperaGrupo de Neurosciencias de Antioquia, Sede de Investigación Universitaria SIU, Medellín, Colombia.
Colin L MastersFlorey Institute and The University of Melbourne, Melbourne, Victoria, Australia.
John C MorrisDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
James M NobleDepartment of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and GH Sergievsky Center, Columbia University, New York, New York, USA.
Alan E RentonDepartment of Genetics and Genomic Sciences and Nash Family Dept of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jee Hoon RohDepartments of Neurology and Physiology, Korea University College of Medicine, Seoul, South Korea.
Matthew P FroschMassGeneral Institute for Neurodegenerative Diseases, Neuropathology Service, Massachusetts General Hospital, Boston, Massachusetts, USA.
C Dirk KeeneDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Catriona McLeanDepartment of Anatomical Pathology, AlfredHealth, Melbourne, Victoria, Australia.
Raquel Sanchez-ValleAlzheimer's Disease and Other Cognitive Disorders Unit, Service of Neurology, Hospital Clinic de Barcelona, FRCB-IDIBAPS, Barcelona, Spain.
Peter R SchofieldNeuroscience Research Australia, Sydney, New South Wales, Australia.
Charlene Supnet-BellDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Chengjie XiongDivision of Biostatistics, Washington University School of Medicine, Saint Louis, Missouri, USA.
Armin GieseModag GmbH, Wendelsheim, Germany.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Randall J BatemanDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Eric McDadeDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA.
Dominantly Inherited Alzheimer Network
Piero ParchiDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.ORCID 0000-0002-9444-9524
Washington University in St. Louis · USGerman Center for Neurodegenerative Diseases · DEIstituto delle Scienze Neurologiche di Bologna · ITIcahn School of Medicine at Mount Sinai · USAlzheimer’s Disease Neuroimaging Initiative · USAsan Medical Center · KRBrown University · USFundación para la Lucha contra las Enfermedades Neurológicas de la Infancia · ARGeneral Motors (Germany) · DEHarvard University · USHospital Clínic de Barcelona · ESJacksonville College · USKorea University · KRLund University · SEMassachusetts General Hospital · USThe University of Melbourne · AUUK Dementia Research Institute · GBUniversity of Bologna · ITUniversity of Exeter · GBUniversity of Pittsburgh · US
Funding
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MResearch Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carolyn Wei Zhu · 2020 to 2026
$31.0MResearch Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7MGenetic basis of neuropsychiatric symptoms in Alzheimer's diseaseU01AG079850 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gary Wayne Beecham, Edward D Huey · 2023 to 2026
$3.0MNeuroanatomical associations with the factor structure underlying neuropsychiatric symptoms in Alzheimer's diseaseR01AG062268 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HUEY, EDWARD D · 2018 to 2022
$2.5MUsing RDoC Negative and Positive Valence Paradigms to Investigate the Mechanisms of Neuropsychiatric Symptoms (NPS) in Alzheimer's Disease and Related DementiasR01MH120794 · NIMH · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HUEY, EDWARD D · 2019 to 2023
$2.1MAlzheimer's Association SG-20-690363-DIAN LATAMBMBF - German Ministry for research and Education (FKZBMBF - German Ministry for research and Education FKZ161L0214B,FKZ161L0214CCLINSPECT-M)Canadian Consortium of Neurodegeneration and Aging, Brain Canada FoundationCIHRDominantly Inherited Alzheimer Network U19AG032438German Center for Neurodegenerative DiseasesGerman Research Foundation under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (SyNergy) EXC2145SyNergy-ID390857198Japan Agency for Medical Research and DevelopmentKorea Dementia Research Center HU21C0066Ministero della Salute RF-2021-12374386NextGenerationEU, Italian Ministry of University and Research, National Recovery and Resilience Plan PE0000006NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066514NIA NIH HHS R01 AG062268NIA NIH HHS U01 AG079850NIA NIH HHS U19 AG032438NIMH NIH HHS R01 MH120794Raul Carrea Institute for Neurological ResearchResearch and Development Grants for DementiaSpanish Institute of Health Carlos III
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 ≈ 50% of AD and ADAD brains.
methodsUsing 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.
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 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.
Indexed as
alpha-SynucleinAlzheimer DiseaseLewy BodiesAgedAmyloid beta-PeptidesBrainDisease ProgressionFemaleHumansMaleMiddle AgedMutationalpha-SynucleinAmyloid beta-Peptidesalpha‐synuclein seed amplification assayDominantly Inherited Alzheimer NetworkLewy body pathologyreal‐time quaking‐induced conversion
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