The AT(N) framework for Alzheimer's disease in adults with Down syndrome

Abstract

The National Institute on Aging in conjunction with the Alzheimer's Association (NIA-AA) recently proposed a biological framework for defining the Alzheimer's disease (AD) continuum. This new framework is based upon the key AD biomarkers (amyloid, tau, neurodegeneration, AT[N]) instead of clinical symptoms and represents the latest understanding that the pathological processes underlying AD begin decades before the manifestation of symptoms. By using these same biomarkers, individuals with Down syndrome (DS), who are genetically predisposed to developing AD, can also be placed more precisely along the AD continuum. The A/T(N) framework is therefore thought to provide an objective manner by which to select and enrich samples for clinical trials. This new framework is highly flexible and allows the addition of newly confirmed AD biomarkers into the existing AT(N) groups. As biomarkers for other pathological processes are validated, they can also be added to the AT(N) classification scheme, which will allow for better characterization and staging of AD in DS. These biological classifications can then be merged with clinical staging for an examination of factors that impact the biological and clinical progression of the disease. Here, we leverage previously published guidelines for the AT(N) framework to generate such a plan for AD among adults with DS.

Keywords: Alzheimer's disease; Down syndrome; biomarkers.

FIGURE 1

Estimated prevalence of A/T(N) positivity across clinical diagnoses. We estimate that between ages 35 to 55 years, there will be 80% A+, 40% T+, and 10% (N)+ for cognitively stable adults with Down syndrome (DS); 80% A+, 60% T+, and 20% (N)+ for mild cognitive impairment (MCI)‐DS; and 80% A+, 80% T+, and 60% (N)+ for the dementia in DS group. A+ = elevated brain amyloid, T+ = tau pathology present, (N) = neurodegeneration present