AT(N) biomarker profiles and Alzheimer's disease symptomology in Down syndrome

Sigan L. Hartley, Benjamin Handen, Dana Tudorascu, Laisze Lee, Annie Cohen, Emily K. Schworer, Jamie C. Peven, Matthew Zammit, William Klunk, Charles Laymon, Davneet Minhas, Weiquan Luo, Shahid Zaman, Beau Ances, Gregory Preboske, Bradley T. Christian

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

INTRODUCTION: Down syndrome (DS) is a genetic cause of early-onset Alzheimer's disease (AD). The National Institute on Aging–Alzheimer's Association AT(N) Research Framework is a staging model for AD biomarkers but has not been assessed in DS. METHOD: Data are from the Alzheimer's Biomarker Consortium–Down Syndrome. Positron emission tomography (PET) amyloid beta (Aβ; 15 mCi of [11C]Pittsburgh compound B) and tau (10 mCi of [18F]AV-1451) were used to classify amyloid (A) –/+ and tau (T) +/–. Hippocampal volume classified neurodegeneration (N) –/+. The modified Cued Recall Test assessed episodic memory. RESULTS: Analyses included 162 adults with DS (aged M = 38.84 years, standard deviation = 8.41). Overall, 69.8% of participants were classified as A–/T–/(N)–, 11.1% were A+/T–/(N)–, 5.6% were A+/T+/(N)–, and 9.3% were A+/T+/(N)+. Participants deemed cognitively stable were most likely to be A–T–(N)– and A+T–(N)–. Tau PET (T+) most closely aligning with memory impairment and AD clinical status. DISCUSSION: Findings add to understanding of AT(N) biomarker profiles in DS. Highlights: Overall, 69.8% of adults with Down syndrome (DS) aged 25 to 61 years were classified as amyloid (A)–/tau (T)–/neurodegeneration (N)–, 11.1% were A+/T–/(N)–, 5.6% were A+/T+/(N)–, and 9.3% were A+/T+/(N)+. The AT(N) profiles were associated with clinical Alzheimer's disease (AD) status and with memory performance, with the presence of T+ aligned with AD clinical symptomology. Findings inform models for predicting the transition to the prodromal stage of AD in DS.

Original languageEnglish
Pages (from-to)366-375
Number of pages10
JournalAlzheimer's and Dementia
Volume20
Issue number1
DOIs
StatePublished - Jan 2024

Keywords

  • ATN
  • Alzheimer's
  • Down syndrome
  • adults
  • amyloid
  • biomarker
  • cognitive
  • dementia
  • hippocampal
  • imaging
  • magnetic resonance imaging
  • memory
  • positron emission tomography
  • tau

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