AMS Seminar: Zheyu Wang (JHMI) @ Whitehead 304

Title: Latent variable models for biomarkers of Alzheimer’s disease
Abstract:  Accumulating evidence suggests that the initiation of Alzheimer’s disease (AD) pathogenic process precedes the first symptoms by a decade or more. The recognition of this decade-long asymptomatic stage has greatly impact AD research and therapeutic development to focus on the preclinical stage of AD pathogenic process, at which time disease-modifying therapy is more likely to be effective. On the other hand, the decade-long preclinical stage imposes a major challenge in investigating biomarkers for early AD detection. The challenge is two-fold. Firstly, the unobservable disease status leads to challenges in evaluating the potential diagnostic capacity of AD biomarkers. Clinical diagnoses are often used in current evaluation, but they are known to be error-prone, especially in the early course of the disease. In addition, the clinical diagnosis is often based on or provide an unfair advantage to current standard tests. Therefore, they can mask the prognostic value of a useful biomarker, especially when the biomarker is much more accurate than the standard tests. Since AD pathophysiology has been recognized as a multidimensional process that involves amyloid deposition, neurofibrillary tangles, and neurodegeneration among other aspects, we proposed a latent variable model to study the underlying AD pathophysiology process revealed by multidimensional markers. Secondly, the unobservable disease process also leads to challenges in understanding the ordering and shape of AD biomarker cascade, which is critical for early detection and therapeutic development yet is still under great debate. I will present a work-in-progress that attempts to inform this debate and outline a model that considers continuous latent disease progression.