Amyloid time: Quantifying the onset of abnormal biomarkers and cognitive impairment along the Alzheimer’s disease continuum

Background Quantifying the temporal progression of key pathophysiological events in Alzheimer’s disease is crucial for staging disease, dementia risk assessment, and informing clinical trials. This work extends a novel algorithm (sampled iterative local linear approximation; SILLA) developed modeling PET trajectories to: 1) generate unified CSF amyloid accumulation timeline, 2) characterize biomarker cognitive changes AD. Method 941 participants from Wisconsin Registry Prevention, Disease Research Center, Statins Healthy, At-Risk Adults: Impact on Amyloid Regional Perfusion studies underwent [C-11]PiB and/or lumbar puncture; subset [F-18]MK-6240 anatomical MRI using standardized protocols (Table 1). burden was quantified cortical PiB DVR Aβ42/40. Time, as years Aβ42/40 positivity, estimated by simultaneously an extension SILLA method 248 with both measurements. biomarkers measured exploratory Roche NeuroToolKit assays, imaging biomarkers, impairment (global CDR, CDR SOB, diagnosis) were plotted function Time. Time between AD LOWESS curves positivity thresholds each scores. Result Figure 1 depicts thresholds. suggested Aβ+, T+, CDR=0.5, CDR=1 occurred 4.0, 12.0, 13.8, 17.7, 22.0 following (Figure 2, Table 2). Heterogeneity observed tau levels relative to individual cases. Those worsening generally had high at least one T+ biomarker. Conclusion based combined provides way quantify duration exposure earliest pathophysiologic onset within individuals. enables characterization time events, which could inform prognosis, identify intervention timing therapies, enable exploration mechanisms related resistance resilience.