This is an optional sub-study that will enroll participants from the LIFE-DSR parent protocol. Participants will undergo assessments at two timepoints, including: additional blood samples for PBMC and RNA extraction, as well as a lumbar puncture for collection of CSF, and/or MRI and tau PET imaging. Sub-study visits will be scheduled around a similar calendar-day as the parent protocol study visits (e.g., Month (M) 0 (M0) and M16, or M16 and M32).
This is an optional sub-study that will enroll participants from the LIFE-DSR parent protocol. Participants will undergo assessments at two timepoints, including: additional blood samples for PBMC and RNA extraction, as well as a lumbar puncture for collection of CSF, and/or MRI and tau PET imaging. Sub-study visits will be scheduled around a similar calendar-day as the parent protocol study visits (e.g., Month (M) 0 (M0) and M16, or M16 and M32). The aim is to increase knowledge of biomarkers of interest in DS-AD clinical progression and perform deep immunophenotyping of PBMC samples. Intervention studies in people with DS depend upon determining the optimal age for treatments to be given, by identifying or developing reliable outcome measures that are most sensitive to decline and discovering biomarkers most closely related to disease progression. For tau deposition, the aim of this study is to ascertain the degree and distribution of tau pathology in DS as a function of age using tau PET, and to determine the longitudinal progression of that pathology. As such, enrichment of the study population included in the tau PET sub-study for presence of tau PET positive scans, and in particular tau PET scans in the earliest stages of positivity, is desirable. Accomplishing this may require flexibility in recruitment, including adjustments of age eligibility as a response to emerging new information in the sub-study population as the study proceeds. PET images will be reviewed in near real-time to enable adaption of the age strata based on the presence or absence of tau PET signal. All the above endpoints will be acquired with informed consent and assent. All data is intended for research purposes only and associated clinical data will be stored securely. Participants will have the option to participate in: * LP to collect CSF and venipuncture to collect a blood sample OR * Imaging (MRI and tau PET) and venipuncture to collect a blood sample OR * Both * LP to collect CSF and venipuncture to collect a blood sample AND * Imaging (MRI and tau PET).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
5
\[18F\]MK-6240 will be synthesized, purified, and formulated at the local radiochemistry synthesis laboratory and will be administered as a sterile, pyrogen-free solution by IV injection.
Barrow Neurological Institute
Phoenix, Arizona, United States
Primary Outcome Measure to establish a biobank specifically for DS participants
CSF AD biomarkers measured longitudinally at approximately Month 0 and Month 16 or Month 16 and Month 32. Establish a biobank specific to DS to receive, store and distribute biospecimens supporting future Omics, biomarker analyses, epigenetic studies, and genotyping. Biomarker candidates will be determined when the study ends and may include primary analytes such as AB42, AB40, AB42/40 ratio, t-tau, p-tau, NfL. Evaluate prespecified CSF biomarkers using technically validated immunoassays on the Quanterix, Mesoscale and Abcam Fireplex Cytokine assay platforms. Biomarker candidates will be determined when the study ends and may include primary analytes such as AB42, AB40, AB42/40 ratio, sAPP, sAPPB, t-tau, p-tau, soluble-TREM2, NfL, GFAP, UCHL1, Tau.
Time frame: Month 0 and Month 16 or Month 16 and Month 32
Primary Outcome to ascertain the degree and distribution of tau pathology in DS as a function of age using tau PET
Burden of total and regional tau deposition, relative to baseline, as measured by \[18F\]MK-6240 uptake. This outcome will provide information regarding: Expected rates of change given baseline amyloid and tau burden, The sample sizes required to detect a reduction in the rate of accumulation at different stages of AD, and Homogeneity and heterogeneity in tau spatial distribution at different stages of AD progression. Correlate the tau PET imaging data with the cognitive, behavioral, functional assessments and medical history data collected in the LIFE-DSR parent protocol to better establish the stage of AD for each participant.
Time frame: Month 0 and Month 16 or Month 16 and Month 32
Secondary Outcome is to increase knowledge of biomarkers of interest in DS-AD clinical progression and perform deep immunophenotyping of PBMC and plasma samples.
The secondary outcome measures include changes relative to baseline compared to AD plasma biomarkers such as A42, A40, NfL, and p-tau 217 and genetic biomarkers of risk such as APOE Conduct deep immunophenotyping of peripheral blood mononuclear cells (PBMCs) Determine within-participant and between-participant variability of specific biomarker candidates in the plasma, PBMCs, CSF and CSF resident immune cells collected at two time points approximately 16 months apart. Month 0 and Month 16 or Month 16 and Month 32
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Time frame: Month 0 and Month 16 or Month 16 and Month 32