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Editorial
July 6, 2021

APOE ε4 Association With Cognition and Alzheimer Disease Biomarkers in Down Syndrome—Implications for Clinical Trials and Treatments for All

Author Affiliations
  • 1Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine
  • 3Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St Louis, Missouri
JAMA Neurol. Published online July 6, 2021. doi:10.1001/jamaneurol.2021.1649

Down syndrome (DS) is the largest genetically determined form of early-onset Alzheimer disease (AD). Adults with DS develop AD pathology by 40 years of age mainly because of overexpression of the APP gene on chromosome 21 that results in the early accumulation of amyloid-β (Aβ) plaques and cerebral amyloid angiopathy followed by tau pathology, neuroinflammation, and brain atrophy.1 The age at which people with DS convert to AD-related cognitive impairment varies from younger than 50 years to older than 70 years.2 However, little is known regarding biomarkers that may help to identify the age at onset of cognitive decline during this preclinical phase of AD in DS.

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