Alzheimer’s Disease: Biomarkers and Progression

Biomarker-informed prediction and trial methodology for Alzheimer’s disease and mild cognitive impairment

2026-06-07 18:16 PDT

Overview

Plasma and cerebrospinal fluid biomarkers have transformed Alzheimer’s disease research: p-tau 217, amyloid-beta 42/40, GFAP, and NfL now provide biological staging that supplements and in some cases supplants clinical rating scales as trial endpoints and eligibility criteria. This program examines biomarker-informed prediction of disease progression, the statistical modeling of biomarker trajectories, and the design of trials that exploit biomarker stratification to improve power.

The empirical foundation is access to data from the Alzheimer’s Disease Cooperative Study (ADCS) – a network of more than 70 research sites that has conducted landmark trials of donepezil, vitamin E, and other agents – together with the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the National Alzheimer’s Coordinating Center (NACC).

Papers in development

  • Prognostic value of plasma p-tau 217 and its APOE4 interaction for time-to-progression from mild cognitive impairment to clinical Alzheimer’s disease.

  • Concomitant medication exposure as a predictor of MCI-to-AD conversion: ensemble machine learning analysis replicated across three multi-site cohorts.

  • Why age fails to predict MCI-to-AD conversion in clinical cohorts: a cross-cohort mediation and collider-bias analysis.

  • Plasma GFAP longitudinal trajectories in blast-exposed veterans: parametric and nonparametric analysis of treatment effects.

Methods

Survival analysis (Cox regression); time-to-event modeling with biomarker interaction terms; AUROC estimation and cross-cohort comparison; ensemble machine learning (gradient boosting, random forests); multiple imputation via mice; LASSO variable selection via glmnet; nonlinear spline effects; ggplot2-based visualization of AD-specific outcomes.

Software

  • zzlongplot – Longitudinal plotting for biomarker trajectories and clinical endpoints in AD trials.
  • zztable1 – Cohort descriptive tables for multi-site AD studies.

Publications

The full publications list filtered by alzheimers-disease or biomarkers provides the relevant record, which includes methodological and applied work conducted through ADCS spanning more than two decades.