Sigan Hartley, PhD – Slide of the Week

Sigan Hartley, PhD – Slide of the Week

Title: AT(N) biomarker profiles and Alzheimer’s disease in People with Down syndrome

Legend: (1) Percentage of adults with Down syndrome (N = 162) in each age group by clinical status and AT(N) biomarker status.  A = PET Aβ, T = tau PET, and (N) = hippocampal volume. MCI-DS = mild cognitive impairment – Down syndrome. (2) Association between PET Aβ and performance on the modified Cued Recall Test (mCRT) by T and N status in the sample of adults with Down syndrome.

Citation: Hartley, S. L., Handen, B., Tudorascu, D., Lee, L., Cohen, A., Schworer, E. K., Peven, J. C., Zammit, M., Klunk, W., Laymon, C., Minhas, D., Luo, W., Zaman, S., Ances, B., Preboske, G., Christian, B. T., & Alzheimer Biomarker Consortium – Down Syndrome (2023). AT(N) biomarker profiles and Alzheimer’s disease symptomology in Down syndrome. Alzheimer’s & Dementia, 10.1002/alz.13446. Advance online publication.

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 [11 C]Pittsburgh compound B) and tau (10 mCi of [18 F]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. Keywords – ATN; Alzheimer’s; Down syndrome; adults; amyloid; biomarker; cognitive; dementia; hippocampal; imaging; magnetic resonance imaging; memory; positron emission tomography; tau.

About the Lab: The Hartley Lab examines the individual resources and family contexts underlying positive well-being in individuals with developmental disabilities and their families.

Investigator: Sigan Hartley, PhD

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