The Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS): A 10-year report

doi:10.1002/alz.70294

The Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS): A 10-year report

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16 Scopus citations

Abstract

INTRODUCTION: Virtually all adults with Down syndrome (DS) will accumulate the neuropathologies associated with Alzheimer's disease (AD) by age 40, with the majority having a clinical dementia diagnosis by their middle 50s. METHODS: This paper complements a 2020 publication describing the Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS) methodology by highlighting protocol changes since initial funding in 2015. It describes available clinical, neuropsychological, neuroimaging, and biofluid data and bio-specimen repository. Ten years of accomplishments are summarized. RESULTS: Over 500 adults with DS and 59 sibling controls have been enrolled since 2015 with nearly 800 follow-up visits. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted; multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. DISCUSSION: ABC-DS is the largest U.S.-based, multi-site (including the United Kingdom and Puerto Rico), longitudinal biomarker initiative to target adults with DS at risk for AD. Highlights: The Alzheimer's Biomarker Consortium—Down Syndrome (ABC-DS) is entering its 10th year. Over 500 adults with Down syndrome (DS) and 59 sibling controls have been enrolled. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted. Multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. It is positioned to continue to make substantial contributions to the DS field.

Original language	English
Article number	e70294
Journal	Alzheimer's and Dementia
Volume	21
Issue number	5
DOIs	https://doi.org/10.1002/alz.70294
State	Published - May 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

The Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) is funded by the National Institute on Aging and the National Institute for Child Health and Human Development (U01 AG051406, U01 AG051412, U19 AG068054) and the Investigation of Co-occurring conditions across the Lifespan to Understand Down syndrome (NIH INCLUDE Project). The work contained in this publication was also supported through the following National Institutes of Health Programs: The Alzheimer's Disease Research Centers Program (P50 AG008702, P30 AG062421, P50 AG016573, P50 AG005133, P50 AG005681, P30 AG062715, P30 AG066519, P30 AG066468 and P30 AG072973), the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program (P50 HD105353), the National Center for Advancing Translational Sciences (UL1 TR001873, UL1 TR002373, UL1 TR001414, UL1 TR001857, UL1 TR002345, UL1 TR002366), the National Centralized Repository for Alzheimer Disease and Related Dementias (U24 AG21886), and DS-Connect (The Down Syndrome Registry) supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). In Cambridge, UK, this research was supported by the NIHR Cambridge Biomedical Research Centre and the Windsor Research Unit, CPFT, Fulbourn Hospital Cambridge, UK. The authors are grateful to the ABC-DS study participants, their families and care providers, and the ABC-DS research and support staff for their contributions to this study. This manuscript has been reviewed by ABC-DS investigators for scientific content and consistency of data interpretation with previous ABC-DS study publications. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the CPFT, the NIHR, or the UK Department of Health and Social Care *Alzheimer's Biomarker Consortium- Down Syndrome (ABC-DS) Investigators: Beau M. Ances, MD PhD; Howard F. Andrews, PhD; Karen Bell, MD; Rasmus M. Birn, PhD; Adam M. Brickman, PhD; Peter Bulova, MD; Jeff Burns, MD; Amrita Cheema, PhD; Kewei Chen, PhD; Bradley T. Christian, PhD; Isabel Clare, PhD; Ann D. Cohen, PhD; Eric W. Doran, MS; Tatiana M. Foroud, PhD; Benjamin L. Handen, PhD; Jordan Harp, PhD; Sigan L. Hartley, PhD; Elizabeth Head, PhD; Denise Head, PhD; Christy Hom, PhD; Lawrence Honig, MD; Milos D. Ikonomovic, MD; Sterling C Johnson, PhD; M. Ilyas Kamboh, PhD; David Keator, PhD; Julia K. Kofler, MD; William Charles Kreisl, MD; Sharon J. Krinsky-McHale, PhD; Florence Lai, MD; Patrick Lao, PhD; Charles Laymon, PhD; Joseph Hyungwoo Lee, PhD; Ira T. Lott, MD; Victoria Lupson, PhD; Mark Mapstone, PhD; Davneet Singh Minhas, PhD; Neelesh Nadkarni, MD; Sid O'Bryant, PhD; Deborah Pang, MPH; Melissa Petersen, PhD; Julie C. Price, PhD; Lauren Ptomey, PhD; Margaret Pulsifer, PhD; Michael S. Rafii, MD PhD; Herminia Diana Rosas, MD; Frederick Schmitt, PhD; Nicole Schupf, PhD; Wayne P. Silverman, PhD; Dana L. Tudorascu, PhD; Rameshwari Tumuluru, MD; Badri Varadarajan, PhD; Michael A. Yassa, PhD; Shahid Zaman, MD PhD; Fan Zhang, PhD. NIA/NICHD: UO1 AG051406, UO1 AG051412, and U19 AG068054. All other authors report no declarations of interest. Currently (as of February 27, 2025) over 200 peer‐reviewed research papers (including a 2020 special issue of ), a book, 10 book chapters, and hundreds of conference presentations and posters have been published or presented using ABC‐DS data. In addition, with 192 data requests from external investigators, a number of papers have been published or are being prepared involving ABC‐DS data. During the past 10 years, dozens of doctoral and post‐doctoral students have been supported in fields including genetics, biostatistics, psychology, neuroimaging, and neuropathology through ABC‐DS. ABC‐DS data has served as the basis for three NIH‐funded K training awards, “Estimating daily movement for the prevention of Alzheimer's disease in Down syndrome” (K01AG083130; Awardee: Helsel; Mentors: Hartley, Ptomey, Burns), “Toward a neuroscientific understanding of the interaction between Down syndrome and Alzheimer's disease pathology” (K01AG083224; Awardee: Bruno; Mentor: Mapstone), and “Remote assessments for Alzheimer's disease cognitive decline in adults with Down syndrome” (K99AG084738; Awardee: Schworer; Mentors: Hartley, Handen, Petersen), two F training awards, “Weight, Inflammation, and Alzheimer's Disease in Down syndrome” (F31AG085730; Fellow: Fleming; Mentors: Hartley, Christian, Mapstone, Ptomey) and “Synergistic contributions of cerebrovascular disease and neuroinflammation to Alzheimer's disease in adults with Down syndrome” (F31AG090091; Fellow: Edwards: Mentors: Brickman, Head, Wilcock), an Alzheimer's Association Research Fellowship to Promote Diversity (23AARFD‐1022715; Awardee: Aguilar; Mentor: Head), a Jerome Lejeune Foundation grant (Awardee: Aguilar; Mentor: Head), and a Brightfocus Foundation Grant (BFF A2022021F; Awardee: Sordo; Mentor: Head). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring The Alzheimer's Biomarkers Consortium–Down Syndrome (ABC‐DS) is funded by the National Institute on Aging and the National Institute for Child Health and Human Development (U01 AG051406, U01 AG051412, U19 AG068054) and the Investigation of Co‐occurring conditions across the Lifespan to Understand Down syndrome (NIH INCLUDE Project). The work contained in this publication was also supported through the following National Institutes of Health Programs: The Alzheimer's Disease Research Centers Program (P50 AG008702, P30 AG062421, P50 AG016573, P50 AG005133, P50 AG005681, P30 AG062715, P30 AG066519, P30 AG066468 and P30 AG072973), the Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program (P50 HD105353), the National Center for Advancing Translational Sciences (UL1 TR001873, UL1 TR002373, UL1 TR001414, UL1 TR001857, UL1 TR002345, UL1 TR002366), the National Centralized Repository for Alzheimer Disease and Related Dementias (U24 AG21886), and DS‐Connect (The Down Syndrome Registry) supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). In Cambridge, UK, this research was supported by the NIHR Cambridge Biomedical Research Centre and the Windsor Research Unit, CPFT, Fulbourn Hospital Cambridge, UK. The authors are grateful to the ABC‐DS study participants, their families and care providers, and the ABC‐DS research and support staff for their contributions to this study. This manuscript has been reviewed by ABC‐DS investigators for scientific content and consistency of data interpretation with previous ABC‐DS study publications. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the CPFT, the NIHR, or the UK Department of Health and Social Care DS‐AD is likely the single greatest impediment to extending life expectancy of adults with DS beyond their 60s. While significant gains have been made during the past 20–30 years toward increasing understanding of the causes, risk factors, and potential treatment of sporadic AD, the DS population has generally been excluded from this work. Important early work in DS‐AD was conducted by a small number of eminent researchers beginning in the late 1980s. Subsequent funding opportunities for this area of research began to increase significantly approximately 15 years ago with a number of parallel research efforts in Europe and the United States, including work by a consortium of European Universities and hospitals (Horizon21), efforts funded by the LuMind Foundation (LIFE‐DSR), and the NIA/NICHD funded multicenter study of biomarkers of AD in adults with DS (the Alzheimer's Biomarker Consortium – Down Syndrome [ABC‐DS]). In addition, in 2018, the INCLUDE Project (INvestigation of Co‐occurring conditions across the Lifespan to Understand Down syndrome) was launched to support a new trans‐National Institutes of Health (NIH) research initiative on critical health and quality‐of‐life needs for individuals with DS. The National Institute on Aging (NIA) has also recently funded the development of a “trial ready cohort” of adults with DS (TRC‐DS; R61 AG066543) and several active efforts to initiate large‐scale AD prevention trials in DS in the United States and Europe are now underway.

Funders	Funder number
DS-Connect
National Institute on Handicapped Research
BrightFocus Foundation
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Jerome-Lejeune Foundation
Department of Health and Social Care *Alzheimer's Biomarker Consortium- Down Syndrome
Alzheimer's Association
Windsor Research Unit
LIFE‐DSR
Alzheimer's Biomarker Consortium
Fulbourn Hospital
NIHR Cambridge Biomedical Research Centre
LuMind IDSC Foundation
CPFT
Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Centers Program
National Institute on Aging
Down Syndrome Registry
National Institutes of Health (NIH)	P50 AG008702, P30 AG062421, P30 AG072973, P30 AG066468, P50 AG005681, P50 AG005133, P50 AG016573, P30 AG066519, P30 AG062715
National Center for Advancing Translational Sciences (NCATS)	UL1 TR002373, UL1 TR001873, UL1 TR002345, UL1 TR002366, UL1 TR001414, UL1 TR001857
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research	U01 AG051412, U01 AG051406, U19 AG068054
Alzheimer's Disease in Down syndrome	F31AG085730, F31AG090091
National Institute for Child Health and Human Development National Research Service	U01 AG051412, U01 AG051406, U19 AG068054
Association of Black Cardiologists Representative	UO1 AG051406, UO1 AG051412
National Centralized Repository for Alzheimer Disease and Related Dementias	U24 AG21886
Intellectual and Developmental Disabilities Research Center	P50 HD105353

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ABC-DS
Alzheimer's disease
Down syndrome
dementia

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

Access to Document

10.1002/alz.70294

Cite this

@article{335fcd2ddba64cfdb24875a32fdb4960,

title = "The Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS): A 10-year report",

abstract = "INTRODUCTION: Virtually all adults with Down syndrome (DS) will accumulate the neuropathologies associated with Alzheimer's disease (AD) by age 40, with the majority having a clinical dementia diagnosis by their middle 50s. METHODS: This paper complements a 2020 publication describing the Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS) methodology by highlighting protocol changes since initial funding in 2015. It describes available clinical, neuropsychological, neuroimaging, and biofluid data and bio-specimen repository. Ten years of accomplishments are summarized. RESULTS: Over 500 adults with DS and 59 sibling controls have been enrolled since 2015 with nearly 800 follow-up visits. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted; multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. DISCUSSION: ABC-DS is the largest U.S.-based, multi-site (including the United Kingdom and Puerto Rico), longitudinal biomarker initiative to target adults with DS at risk for AD. Highlights: The Alzheimer's Biomarker Consortium—Down Syndrome (ABC-DS) is entering its 10th year. Over 500 adults with Down syndrome (DS) and 59 sibling controls have been enrolled. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted. Multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. It is positioned to continue to make substantial contributions to the DS field.",

keywords = "ABC-DS, Alzheimer's disease, Down syndrome, dementia",

author = "Handen, \{Benjamin L.\} and Mark Mapstone and Sigan Hartley and Howard Andrews and Brad Christian and Lee, \{Joseph H.\} and Dana Tudorascu and Christy Hom and Ances, \{Beau M.\} and Shahid Zaman and Sharon Krinsky-McHale and Brickman, \{Adam M.\} and Rosas, \{H. Diana\} and Annie Cohen and Melissa Petersen and Sid O'Bryant and Harp, \{Jordan P.\} and Frederick Schmitt and Lauren Ptomey and Jeffrey Burns and Lott, \{Ira T.\} and Florence Lai and Wayne Silverman and Charles Laymon and Elizabeth Head",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = may,

doi = "10.1002/alz.70294",

language = "English",

volume = "21",

number = "5",

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T1 - The Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS)

T2 - A 10-year report

AU - Handen, Benjamin L.

AU - Mapstone, Mark

AU - Hartley, Sigan

AU - Andrews, Howard

AU - Christian, Brad

AU - Lee, Joseph H.

AU - Tudorascu, Dana

AU - Hom, Christy

AU - Ances, Beau M.

AU - Zaman, Shahid

AU - Krinsky-McHale, Sharon

AU - Brickman, Adam M.

AU - Rosas, H. Diana

AU - Cohen, Annie

AU - Petersen, Melissa

AU - O'Bryant, Sid

AU - Harp, Jordan P.

AU - Schmitt, Frederick

AU - Ptomey, Lauren

AU - Burns, Jeffrey

AU - Lott, Ira T.

AU - Lai, Florence

AU - Silverman, Wayne

AU - Laymon, Charles

AU - Head, Elizabeth

PY - 2025/5

Y1 - 2025/5

N2 - INTRODUCTION: Virtually all adults with Down syndrome (DS) will accumulate the neuropathologies associated with Alzheimer's disease (AD) by age 40, with the majority having a clinical dementia diagnosis by their middle 50s. METHODS: This paper complements a 2020 publication describing the Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS) methodology by highlighting protocol changes since initial funding in 2015. It describes available clinical, neuropsychological, neuroimaging, and biofluid data and bio-specimen repository. Ten years of accomplishments are summarized. RESULTS: Over 500 adults with DS and 59 sibling controls have been enrolled since 2015 with nearly 800 follow-up visits. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted; multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. DISCUSSION: ABC-DS is the largest U.S.-based, multi-site (including the United Kingdom and Puerto Rico), longitudinal biomarker initiative to target adults with DS at risk for AD. Highlights: The Alzheimer's Biomarker Consortium—Down Syndrome (ABC-DS) is entering its 10th year. Over 500 adults with Down syndrome (DS) and 59 sibling controls have been enrolled. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted. Multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. It is positioned to continue to make substantial contributions to the DS field.

AB - INTRODUCTION: Virtually all adults with Down syndrome (DS) will accumulate the neuropathologies associated with Alzheimer's disease (AD) by age 40, with the majority having a clinical dementia diagnosis by their middle 50s. METHODS: This paper complements a 2020 publication describing the Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS) methodology by highlighting protocol changes since initial funding in 2015. It describes available clinical, neuropsychological, neuroimaging, and biofluid data and bio-specimen repository. Ten years of accomplishments are summarized. RESULTS: Over 500 adults with DS and 59 sibling controls have been enrolled since 2015 with nearly 800 follow-up visits. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted; multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. DISCUSSION: ABC-DS is the largest U.S.-based, multi-site (including the United Kingdom and Puerto Rico), longitudinal biomarker initiative to target adults with DS at risk for AD. Highlights: The Alzheimer's Biomarker Consortium—Down Syndrome (ABC-DS) is entering its 10th year. Over 500 adults with Down syndrome (DS) and 59 sibling controls have been enrolled. More than 900 magnetic resonance imaging (MRI), 800 amyloid positron emission tomography (PET), and 600 tau PET scans have been conducted. Multiple omics data have been generated using over 1100 blood and 100 cerebrospinal fluid (CSF) samples. It is positioned to continue to make substantial contributions to the DS field.

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KW - Alzheimer's disease

KW - Down syndrome

KW - dementia

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AN - SCOPUS:105005402718

SN - 1552-5260

VL - 21

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

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M1 - e70294

ER -

The Alzheimer's Biomarker Consortium–Down Syndrome (ABC-DS): A 10-year report

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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