With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.
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The LIFE-DSR study is funded by the LuMind IDSC Foundation. Eli Lilly provided the analysis of the plasma biomarkers to LuMind IDSC as an in-kind contribution. Samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study.
The data presented in this study are available on request from the corresponding author. The data are not publicly available due to the ongoing nature of the LIFE-DSR natural history study.
The following are available online at https://www.mdpi.com/article/10.3390/jcm10091907/s1, Figure S1: Histograms (diagonal), scatterplots (below diagonal), and Spearman correlations (above diagonal) for biomarkers and clinical data; Figure S2: Linear regression fit of untransformed GFAP on age, using restricted cubic splines with 4 knots and robust standard errors; Figure S3: Linear regression fit of untransformed p-tau 217 on age, using restricted cubic splines with 4 knots and robust standard errors; Figure S4: Linear regression fit of untransformed p-tau 181 on age, using restricted cubic splines with 4 knots and robust standard errors; Figure S5: Linear regression fit of untransformed NfL on age, using restricted cubic splines with 4 knots and robust standard errors; Figure S6: Linear regression fit of untransformed Aβ42/Aβ40 ratio on age, using restricted cubic splines with 4 knots and robust standard errors; Figure S7: Shown are the predictions from linear regressions of each biomarker on age, using restricted cubic splines with 4 knots, and adjusted for APOE e4 carrier status and sex using additive covariates; APOE e4 adjusted to non-carrier and sex adjusted to female.
The above materials are also available for download as the additional file listed at the end of this record.
Hendrix, James A.; Airey, David C.; Britton, Angela; Burke, Anna D.; Capone, George T.; Chavez, Ronelyn; Chen, Jacqueline; Chicoine, Brian; Costa, Alberto C. S.; Dage, Jeffrey L.; Doran, Eric; Esbensen, Anna; Evans, Casey L.; Faber, Kelley M.; Foroud, Tatiana M.; Hart, Sarah; Haugen, Kelsey; Head, Elizabeth; Hendrix, Suzanne; Hillerstrom, Hampus; and Schmitt, Frederick A., "Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study" (2021). Sanders-Brown Center on Aging Faculty Publications. 166.