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Alzheimer's Biomarkers Consortium — Down Syndrome (ABC-DS)

Man with down syndrome

Exploring the Connection Between Down Syndrome and Alzheimer's Disease

The ABC-DS study is a joint study conducted by two groups of research collaborators—Neurodegeneration in Aging Down Syndrome (NiAD) and Alzheimer's Disease in Down Syndrome (ADDS)—and is currently funded at $43 million by the National Institute on Aging (NIA) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of NIH.

Background

Adults with Down syndrome (DS) are at high risk for early onset of Alzheimer's disease (AD). Virtually all adults with DS have neuropathological changes consistent with AD by age 40, including deposition of Aβ in diffuse and neuritic plaques, and most will develop clinical dementia by their late 60s. The high risk for AD has been attributed, at least in part, to triplication and overexpression of the gene for amyloid precursor protein (APP)on chromosome 21, leading to elevated levels of Aβ peptides. However, there is wide variation in age at onset of dementia, ranging from under 40 to over 70 years of age. This range in age suggests that additional genetic, biological, and environmental factors modify the rate and degree of Ab deposition or clearance, and may be important modifiers of risk that accelerate or slow disease progression.

Early diagnosis is critically important given that effective prevention and treatment must precede irreversible neuronal loss. However, early AD-related changes are especially difficult to identify in adults with DS because of variable levels of lifelong cognitive impairments. Thus, development of empirically supported methods for early diagnosis of dementia in DS, biological characterization of the preclinical and early phases of AD, and identification of risk factors for AD progression are critical to the early diagnosis of dementia and for the development of effective intervention and treatment.

Goals and Measures

The overall goals of this study are to:

  • Identify sensitive neuropsychological measures of cognitive decline, imaging, blood-based, and genetic biomarkers associated with transition from normal aging to mild cognitive impairment to clinical dementia in adults with DS
  • Identify critical factors that link cerebral Aβ deposition to neurodegeneration and, ultimately, dementia
  • Understand the relationships between biomarkers and pathways implicated in AD pathogenesis
  • Provide rapid public access to all data, without embargo, and access to the biological samples by qualified scientific investigators

Common core measures, collected at multiple time points to support longitudinal analyses, include:

  • Direct cognitive and functional measures (tests of memory, visual spatial construction, language, executive processing and speed, mental status, and gait)
  • Caregiver questionnaires (queries on functional abilities, mental status, neuropsychiatric symptoms, and dementia screening)
  • Medical and neurological assessments (personal and family health history, medication usage, and a brief physical and neurological examination)
  • Neuroimaging biomarkers (MRI-based measures of cortical thickness and volume, white matter abnormalities and connectivity, as well as amyloid-, tau-, and FDG-PET)
  • Blood-based biomarkers (a proteomics panel with proinflammatory markers, a metabolomics panel, and an assay of plasma Aβ peptides—Aβ40, Aβ42, Aβ40/Aβ42 ratio)
  • Genetic studies (candidate analysis focusing on variants in genes associated with AD and with individual differences in blood-based, imaging, and CSF biomarkers that are found to be associated with clinical disease progression including Aβ42, P181-tau, and total tau)

There will be 3-4 cycles of assessment, at approximately 16-month intervals, over the 5-year study. However, some procedures will only be included in selected cycles.

Recruitment

The NiAD sites will recruit 180 adults with DS (10% with dementia) and 40 sibling controls, age 25 years and older. The ADDS sites will recruit 225-300 adults with DS, 40 years and older.

Share this information with patients and families who may be interested in participating.

Study Sites and Investigators

Neurodegeneration in Aging Down Syndrome (NiAD)

Site Investigator & Study Coordinator
University of Pittsburgh (Coordinating Center), Pittsburgh, PA
Ben Handen, Ph.D., Co-PI
William Klunk, M.D., Ph.D., Co-PI
Cathy Wolfe, Study Coordinator
University of Wisconsin Madison, WI
Brad Christian, Ph.D., Co-PI
Renee Makuch, Study Coordinator
University of Cambridge Cambridge, UK
Shahid Zaman, M.D., Ph.D., Site PI
Concepcion Padilla, Study Coordinator

 

Alzheimer's Disease in Down Syndrome (ADDS)

Site Investigator & Study Coordinator
Columbia University (Coordinating Center) New York, NY
Nicole Schupf, Ph.D., Co-PI
Deborah Pang, Study Coordinator
Kennedy Krieger Institute/Johns Hopkins Medical Center Baltimore, MD
Wayne Silverman, Ph.D., Co-PI
University of California, Irvine Irvine, CA
Ira Lott, M.D., Co-PI
Eric Doran, Study Coordinator
Alicia Hernandez, Study Coordinator
Harvard/Massachusetts General Hospital Boston, MA
Florence Lai, M.D., Site PI
Diana Rosas, M.D., Site PI
Nusrat Jahan, Study Coordinator
Courtney Jordan, Study Coordinator
The New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY
Sharon Krinsky-McHale, Ph.D., Site PI
Deborah Pang, Study Coordinator
University of North Texas Health Science Center Fort Worth, TX
Sid O'Bryant, Ph.D., Site PI

(Note that enrollment is limited to sites with study coordinators listed)

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