🧫 Experiment Protocol
ClinicalAlzheimer's diseaseAPP, MAPTChilean older adults (n=318) with CU, SCC, MCI, and ADDproposed
This clinical biomarker study evaluated plasma amyloid, tau, and neurodegeneration (ATN) biomarkers in 318 older adults from a Chilean community- and clinic-based cohort to assess their ability to distinguish different stages along the Alzheimer's disease continuum. Participants included cognitively unimpaired (CU) individuals, those with subjective cognitive complaints (SCC), mild cognitive impairment (MCI), and Alzheimer's disease dementia (ADD). The study quantified plasma ATN biomarkers (Aβ42/Aβ40, p-tau217, NfL, and GFAP) using Simoa technology and assessed cognitive performance using standardized neuropsychological tests including the Addenbrooke's Cognitive Examination (ACE), Free and Cued Selective Reminding Test (FCSRT), and Technology–Activities of Daily Living Questionnaire (T-ADLQ). The research aimed to determine whether plasma biomarker combinations could effectively stage AD pathology and examine their clinical associations in an underrepresented Latin American population. Statistical analyses included ANCOVA models to examine group differences and linear regression to evaluate associations with cognitive performance. Additionally, supervised machine-learning models were implemented to classify participants across diagnostic categories based on plasma biomarker profiles.
PRIMARY OUTCOME
Plasma biomarker levels across AD continuum and diagnostic classification accuracy
EXPECTED OUTCOMES
Progressive decline in Aβ42/Aβ40 ratio and elevations in p-tau217 and GFAP across clinical continuum; inverse associations between p-tau217/NfL and cognitive performance
SUCCESS CRITERIA
- Prespecified primary endpoint (Plasma biomarker levels across AD continuum and diagnostic classification accuracy) improves versus control with p < 0.05 or an equivalent corrected threshold used by the study.
- The effect size is biologically meaningful and reproduced across technical/biological replicates or the validation subset.
- Safety, data quality, and missingness remain within protocol-defined bounds so the result is interpretable rather than driven by attrition or assay failure.
PROTOCOL
1. Establish Chilean older adults (n=318) with CU, SCC, MCI, and ADD cohorts for Alzheimer's disease and predefine inclusion, exclusion, and quality-control criteria before intervention. 2. Apply the experimental manipulation described for APP, MAPT, alongside matched control or comparator arms, and document dose, exposure window, and sample timing in a locked protocol log. 3. Measure Plasma biomarker levels across AD continuum and diagnostic classification accuracy together with orthogonal secondary readouts such as molecular, imaging, behavioral, or safety endpoints that are appropriate to the title and study design. 4. Use blinded outcome assessment where feasible, prespecified statistical analysis, and replicate the core readout across biological replicates or an independent validation subset. 5. Interpret results against the baseline study rationale: This clinical biomarker study evaluated plasma amyloid, tau, and neurodegeneration (ATN) biomarkers in 318 older adults from a Chilean community- and clinic-based cohort to assess their ability to distinguish different stages along the Alzheimer's disease cont