The Case for Widening the Scope of Alzheimer’s Disease Models and Biomarkers

Abstract

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder primarily associated with amyloid-beta and tau, but numerous other mechanisms, such as vascular injury, oxidative stress, mitochondrial dysfunction, and inflammation—among many others-- also contribute yet receive comparatively little attention. This opinion paper discusses how this narrow focus limits research through incomplete animal models and biomarkers. While essential, many animal models omit critical aspects of AD’s pathology, further complicating issues in replicating the complexity of the disease and translating findings. In parallel, the development of potential therapies primarily focuses on amyloid-beta, while biomarker classification systems are largely confined to amyloid-beta and tau. Addressing these gaps requires embracing existing comprehensive pathological models and broadening biomarker panels to better capture AD’s heterogeneity. Such an approach would enable the development of personalized, multi-targeted therapeutic strategies that more accurately reflect variability in disease processes among patients.