Bridging prion biology and Alzheimer’s disease: from pathogenic seeds to precision therapeutics

TL;DR

This review explores how prion biology can inform Alzheimer’s disease research, focusing on shared mechanisms and new therapeutic strategies.

Contribution

A novel framework combining prion biology and AD pathogenesis for precision therapeutics is proposed.

Findings

Aβ/tau and PrPSc share conformational features and strain-specific propagation.

Pathogenic seeds spread through neural networks in spatiotemporal patterns.

Prion-based insights offer new biomarkers and therapeutic strategies for AD.

Abstract

Alzheimer’s disease (AD) is characterized by the pathological aggregation of amyloid-beta (Aβ) and tau proteins, which display self-templating propagation reminiscent of the prion protein (PrPSc). Despite these similarities, distinct structural heterogeneities and host interaction mechanisms offer unique avenues for disease-modifying therapies. This review comprehensively synthesizes recent advancements addressing: (1) the conformational commonalities and strain-specificities shared between Aβ/tau and PrPSc; (2) the spatiotemporal dissemination patterns of pathogenic seeds within neural networks; and (3) the development of biomarkers and therapeutic strategies rooted in prion theory. By integrating insights from prion biology with AD pathogenesis, we propose a comprehensive “conformation-propagation-microenvironment” framework for precision intervention, thereby offering a novel paradigm to surmount current therapeutic limitations.

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