AT(N) Biomarker profiles and Alzheimer’s Disease clinical status and memory in adults with down syndrome

Abstract Background Down syndrome (DS) is seen as a genetic form of Alzheimer’s disease (AD). The National Institute on Aging and the Alzheimer’s Association proposed the AT(N) model for classifying AD biomarkers of amyloid (A), tau (T), and neurodegeneration or neuronal injury ([N]) in non‐DS populations. It is not yet known how the AT(N) classification system maps onto AD pathology and symptomology in DS. The goals of the present study were to: 1) examine AT(N) profiles in DS based on PET amyloid‐beta (Aβ) (A), tau PET (T), and hippocampal volume ([N]); and 2) evaluate potential differences in clinical AD status and memory performance by AT(N) profile in DS. Method Analyses included 138 adults with DS (age: M = 39.1, SD = 8.0) enrolled in the Alzheimer’s Biomarker Consortium‐ Down Syndrome study. PET Aβ and tau were assessed using [ 11 C]PiB and [ 18 F]AV‐1451. Structural MRI data was used to index hippocampal volume and adjusted for intracranial volume. Thresholds for elevated (+ vs. ‐) A (Aβ CL >19), T (tau composite SUVr >1.21) and (N) (hippocampal volume < 1 SD from sample mean) were based on prior studies. Clinical AD status (cognitively stable, mild cognitive impairment [MCI‐DS], dementia, and unable to determine) were based on direct measures and caregiver‐report but blind to imaging and biofluid data. The Cued Recall Test was used to assess episodic memory. Result Overall, 66% of participants were A‐/T‐/(N)‐, 14% were A+/T‐/(N)‐, 9% were A+/T+/(N)‐, and 5% were A+/T+/(N)+. The remaining 6% had an alternative profile (e.g. A‐/T‐/(N)+). One‐way analyses of variance indicated a significant difference in age and clinical AD status by A/T/N profile. General linear models controlling for age and premorbid intellectual disability level indicated differences in memory by A/T/(N) profile. Conclusion This study adds to the understanding of AT(N) biomarker profiles in DS and their association with AD symptomology. Clinical AD status of MCI‐DS and dementia and worse memory performance were associated with elevated T and (N), in line with non‐DS populations. The unable to determine status paralleled the MCI and dementia status groups. Findings inform models that predict the transition to AD in DS. aging after age 90.