Genetically determined Alzheimer's disease research advances: The Down Syndrome & Autosomal Dominant Alzheimer's Disease 2024 Conference

Neus Falgàs¹, Lucia Maure-Blesa², Beau Ances³, Lisi Flores-Aguilar⁴, Sigan Hartley⁵, Jason Hassenstab³, M Florencia Iulita⁶, Matthew Janicki^{7

8}, Katherine Koenig⁹, Patrick Lao¹⁰, Johannes Levin^{11

12

13}, Eric McDade³, Laurent Meijer¹⁴, Michael S Rafii¹⁵, Heather M Snyder¹⁶, Raquel Sánchez-Valle¹, Juan Fortea^{2

17

18}; DSAD‐ADAD conference group; Jose Arriola Infante², Mirea Balasa¹, Isabel Barroeta^{2

17}, Nicolas Barthelemy R³, Alexandre Bejanin^{2

17}, Bessy Benejam¹⁸, Beatriz Bosch¹, Angela Bradshaw¹⁹, Maria Carmona-Iragui^{2

17

18}, Ann Cohen²⁰, Aina Comas Albertí¹, Lajos Csincsik²¹, A Claudio Cuello²², Laura Del Hoyo Soriano^{2

17}, Janna Dijkstra²³, Natalie Edwards^{10

24

25}, Sandra Giménez^{2

17

26}, Fernando Gonzalez-Ortiz²⁷, Brian Gordon³, Sara Gutiérrez Fernández²⁸, Benjamin Handen²⁰, Charlotte Jacob²⁹, Erik Johnson³⁰, Charlotte Johansson³¹, Albert Lladó¹, Alberto Lleó^{2

17}, Samuel Morabito⁴, Alejandra O Morcillo-Nieto^{2

17}, Laia Montoliu-Gaya²⁷, Michael Okafor³², Agnes Pérez-Millan¹, Marie Claude Potier³², John Ringman³³, Íñigo Rodríguez-Baz^{2

17}, Eric Rubenstein³⁴, Natalie S Ryan³⁵, André Strydom³⁶, Lidia Vaqué-Alcázar², Lisa Vermunt³⁷, Laura Videla Toro^{2

17

18}, Shahid Zaman³⁸

Affiliations

¹ Alzheimer's Disease and Other Cognitive Disorders Unit, Service of Neurology, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
² Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Sant Antoni Maria Claret, Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain.
³ Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
⁴ Department of Pathology and Laboratory Medicine, University of California, Irvine, California, USA.
⁵ Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁶ Altoida Inc., Washington, District of Columbia, USA.
⁷ Department of Disability and Human Development, University of Illinois Chicago, Chicago, Illinois, USA.
⁸ National Task Group on Intellectual Disabilities and Dementia Practices, Rockport, Maine, USA.
⁹ Imaging Sciences, Imaging Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁰ Gertrude H. Sergievsky Center and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
¹¹ Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
¹² German Center for Neurodegenerative Diseases, Munich, Germany.
¹³ Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
¹⁴ Perha Pharmaceuticals; Centre de Perharidy, Hôtel de Recherche, Roscoff, France.
¹⁵ Alzheimer's Therapeutic Research Institute, USC Keck School of Medicine, San Diego, California, USA.
¹⁶ Division of Medical and Scientific Relations, Alzheimer's Association, Chicago, Illinois, USA.
¹⁷ Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
¹⁸ Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Entresòl, Barcelona, Spain.
¹⁹ Alzheimer Europe, Bertrange, Luxembourg.
²⁰ Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²¹ School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, University Rd, Belfast, UK.
²² McGill University Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
²³ Genomics of Neurodegenerative Diseases and Aging, Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, Netherlands.
²⁴ Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, New York, USA.
²⁵ Department of Neuroscience, Columbia University, New York City, New York, USA.
²⁶ Multidisciplinary Sleep Unit. Respiratory department. Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain.
²⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
²⁸ VIB-KU Leuven Center for Brain & Disease Research, VIB Center for Brain & Disease research, Leuven, Belgium.
²⁹ Laboratory of Neurochemistry and Behaviour, Experimental Neurobiology Unit, University of Antwerp, Antwerpen, Belgium.
³⁰ Department of Neurology, Emory University, Atlanta, Georgia, USA.
³¹ Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Stockholm, Sweden.
³² Sorbonne Université, Institut du Cerveau-Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France Hôpital Pitié, Paris, France.
³³ Department of Neurology, University of Southern California, Los Angeles, California, USA.
³⁴ Department of Epidemiology, Boston University, Boston, Massachusetts, USA.
³⁵ Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, Queen Square, London, UK.
³⁶ Institute of Psychiatry, Psychology, and Neuroscience, King's College London, Strand London, UK.
³⁷ Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University, Amsterdam UMC, Amsterdam, the Netherlands.
³⁸ Department of Psychiatry, University of Cambridge, Cambridge, UK.

PMID: 40604347
PMCID: PMC12221810
DOI: 10.1002/alz.70309

Review

Genetically determined Alzheimer's disease research advances: The Down Syndrome & Autosomal Dominant Alzheimer's Disease 2024 Conference

Neus Falgàs et al. Alzheimers Dement. 2025 Jul.

. 2025 Jul;21(7):e70309.

doi: 10.1002/alz.70309.

Authors

Affiliations

¹ Alzheimer's Disease and Other Cognitive Disorders Unit, Service of Neurology, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
² Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Sant Antoni Maria Claret, Departamento de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain.
³ Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
⁴ Department of Pathology and Laboratory Medicine, University of California, Irvine, California, USA.
⁵ Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁶ Altoida Inc., Washington, District of Columbia, USA.
⁷ Department of Disability and Human Development, University of Illinois Chicago, Chicago, Illinois, USA.
⁸ National Task Group on Intellectual Disabilities and Dementia Practices, Rockport, Maine, USA.
⁹ Imaging Sciences, Imaging Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁰ Gertrude H. Sergievsky Center and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
¹¹ Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.
¹² German Center for Neurodegenerative Diseases, Munich, Germany.
¹³ Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
¹⁴ Perha Pharmaceuticals; Centre de Perharidy, Hôtel de Recherche, Roscoff, France.
¹⁵ Alzheimer's Therapeutic Research Institute, USC Keck School of Medicine, San Diego, California, USA.
¹⁶ Division of Medical and Scientific Relations, Alzheimer's Association, Chicago, Illinois, USA.
¹⁷ Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
¹⁸ Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Entresòl, Barcelona, Spain.
¹⁹ Alzheimer Europe, Bertrange, Luxembourg.
²⁰ Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²¹ School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, University Rd, Belfast, UK.
²² McGill University Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
²³ Genomics of Neurodegenerative Diseases and Aging, Department of Human Genetics, Amsterdam University Medical Center, Amsterdam, Netherlands.
²⁴ Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, New York, USA.
²⁵ Department of Neuroscience, Columbia University, New York City, New York, USA.
²⁶ Multidisciplinary Sleep Unit. Respiratory department. Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain.
²⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
²⁸ VIB-KU Leuven Center for Brain & Disease Research, VIB Center for Brain & Disease research, Leuven, Belgium.
²⁹ Laboratory of Neurochemistry and Behaviour, Experimental Neurobiology Unit, University of Antwerp, Antwerpen, Belgium.
³⁰ Department of Neurology, Emory University, Atlanta, Georgia, USA.
³¹ Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Solna, Stockholm, Sweden.
³² Sorbonne Université, Institut du Cerveau-Paris Brain Institute - ICM, CNRS, APHP, Hôpital de La Pitié Salpêtrière, InsermParis, France Hôpital Pitié, Paris, France.
³³ Department of Neurology, University of Southern California, Los Angeles, California, USA.
³⁴ Department of Epidemiology, Boston University, Boston, Massachusetts, USA.
³⁵ Dementia Research Centre, Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, Queen Square, London, UK.
³⁶ Institute of Psychiatry, Psychology, and Neuroscience, King's College London, Strand London, UK.
³⁷ Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University, Amsterdam UMC, Amsterdam, the Netherlands.
³⁸ Department of Psychiatry, University of Cambridge, Cambridge, UK.

PMID: 40604347
PMCID: PMC12221810
DOI: 10.1002/alz.70309

Abstract

Introduction: The Down syndrome-associated Alzheimer's disease (DSAD) autosomal dominant Alzheimer's disease (ADAD) 2024 Conference in Barcelona, convened under an Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) grant through the Down syndrome and Alzheimer's disease (AD) Professional Interest Area (PIA), brought together global researchers to foster collaboration and knowledge exchange between the fields of DSAD and ADAD.

Methods: This article provides a synthesis review of the conference proceedings, summarizing key discussions on biomarkers, natural history models, clinical trials, and ethical considerations in anti-amyloid therapies.

Results: A total of 211 attendees from 16 countries joined the meeting. Global researchers presented on disease mechanisms, therapeutic developments, and patient care strategies. Discussions focused on challenges and opportunities unique to DSAD and ADAD. Experts emphasized the urgent need for tailored clinical trials for ADAD and DSAD and debated the safety and efficacy of anti-amyloid treatments. Ethical considerations highlighted equitable access to therapies and the crucial role of patient and caregiver involvement.

Discussion: The conference highlighted the importance of inclusive research and collaboration across the genetic forms of AD.

Highlights: Biomarker research and natural history models developed in Down syndrome-associated Alzheimer's disease (DSAD) and autosomal dominant Alzheimer's disease (ADAD) enable the prediction of disease progression not only for DSAD and ADAD, but also for sporadic Alzheimer's disease (AD). -Collaboration and knowledge exchange among researchers across these genetic forms of AD will accelerate our understanding of the pathophysiology and advance preventive trials in DSAD and ADAD. -Tailored clinical trials for DSAD are urgently needed to address specific safety and efficacy concerns. -Inclusive research practices are crucial for advancing treatments and understanding of DSAD and ADAD.

Keywords: Autosomal dominant Alzheimer's disease; Biomarkers; Clinical trials; Down syndrome; Neuroimaging; Pathophysiology.

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Conflict of interest statement

Instituto de Salut Carlos III supported L.M.B. and N.F. and co‐funded by the European Union through the Río Hortega Fellowship “CM23/00291” (L.M.B.) and Juan Rodés grant JR22/00014 (N.F.). N.S.R. acknowledges support from the UK Dementia Research Institute at UCL through UK DRI Ltd, principally funded by the UK Medical Research Council, the UK NIHR UCLH Biomedical Research Centre, and the Dominantly Inherited Alzheimer Network, funded by the National Institute on Aging. L.M. is funded by grants from the “Fondation Jérôme Lejeune”, the “Agence Nationale de la Recherche (ANR)” (DYRK‐DOWN, TRANSBIOROYAL and KINHIB‐DIAB projects), France 2030 (i‐Nov vague 9, Leucettinib‐21 project), and Bpifrance (EUROSTARS, T2DiaCURE project), the European Union's Horizon 2020 research and innovation program (GO‐DS21 project) and the European Innovation Council (EIC) Accelerator Program (DOWN‐AUTONOMY project, 190138295). Alzheimer's Association ISTAART Conference Support Award. H.M.S. is a full‐time employee of the Alzheimer's Association, and their spouse is an employee at Abbott Labs in an unrelated field. L.V.A. was supported by Instituto de Salud Carlos III through the Sara Borrell Postdoctoral Fellowship “CD23/00235”. M.C.I. acknowledges support from the Alzheimer's Association and Global Brain Health Institute (GBHI_ALZ‐18‐543740), the Jérôme Lejeune Foundation (#1913 Cycle 2019B), the Societat Catalana de Neurologia (Premi Beca Fundació SCN 2020). I.R.B. was supported by Instituto de Salud Carlos III through the Río Hortega Fellowship “CM22/00052” and co‐funded by the European Union. J.E.A.I. was supported by Instituto de Salud Carlos III through the Río Hortega Fellowship “CM22/00219” and co‐funded by the European Union. J.A. was supported by Instituto de Salud Carlos III through the Río Hortega Fellowship “CM21/00243” and co‐funded by the European Union. L.M.B. was supported by Instituto de Salud Carlos III through the Río Hortega Fellowship “CM23/00291” and co‐funded by the European Union. A.B. acknowledges support from Instituto de Salud Carlos III through the Miguel Servet grant “CP20/00038” and co‐funded by the European Union, and the Alzheimer's Association “AARG‐22‐923680.” L.D.H.S. acknowledges support from Instituto de Salud Carlos III through the Miguel Servet grant CP24/00112 and co‐funded by the European Union, and the the Jérôme Lejeune Foundation (2326 ‐ GRT‐2024A). The conference was funded by grants from the Alzheimer's Association through the International Society to Advance Alzheimer's Research and Treatment (ISTAART) Grant Program for Conferences and Convenings (IGPCC) and the Pasqual Maragall Foundation, with the support of the pharmaceutical industry. J.F. reported receiving personal fees for service on the advisory boards, adjudication committees, or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Eisai, Esteve, Fujirebio, Ionis, Laboratorios Carnot, Life Molecular Imaging, Lilly, Lundbeck, Novo Nordisk, Perha, Roche, Zambón, and outside the submitted work. D.A., A.L., and J.F. reports holding a patent for markers of synaptopathy in neurodegenerative disease (licensed to ADx, EPI8382175.0). S.G. reported receiving personal fees for service on the advisory boards, speaker honoraria, or educational activities from Esteve, Indorsia, and Biojen. MCI reported receiving personal fees for service on the advisory boards, speaker honoraria, or educational activities from Esteve, Lilly, Neuraxpharm, Adium, and Roche. Author disclosures are available in the Supporting Information.

Figures

**FIGURE 1**
DSAD‐ADAD Conference summary infographic: Key statistics. ADAD, autosomal dominant Alzheimer's disease; DSAD, Down syndrome‐associated Alzheimer's disease.

**FIGURE 2**
Call for action in the DSAD‐ADAD field. Created in https://BioRender.com. ADAD, autosomal dominant Alzheimer's disease; DSAD, Down syndrome‐associated Alzheimer's disease

See this image and copyright information in PMC

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Genetically determined Alzheimer's disease research advances: The Down Syndrome & Autosomal Dominant Alzheimer's Disease 2024 Conference

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Genetically determined Alzheimer's disease research advances: The Down Syndrome & Autosomal Dominant Alzheimer's Disease 2024 Conference

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Conflict of interest statement

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