Diamagnetic Signature of Beta-Amyloid (Aβ) and Tau (τ) Tangle Pathology in Alzheimer's Disease: A Review

Abstract

The complex interplay between diamagnetic and paramagnetic substances within the brain, particularly in the context of Alzheimer's disease (AD), offers a rich landscape for investigation using advanced quantitative neuroimaging techniques. Although conventional approaches have focused on the paramagnetic properties of iron, emerging and promising research has highlighted the significance of diamagnetic signatures associated with beta-amyloid (Aβ) plaques and Tau (τ) protein aggregates. Quantitative susceptibility mapping (QSM) is a complex post-processing technique that visualizes and characterizes these subtle alterations in brain border tissue composition, such as the gray–white matter interface. Through voxel-wise separation of the contributions of diamagnetic and paramagnetic sources, QSM enabled the identification and quantification of Aβ and τ aggregates, even in the presence of iron. However, several challenges remain in utilizing diamagnetic signatures of Aβ and τ for clinical applications. These include the relatively small magnitude of the diamagnetic signal compared to paramagnetic iron, the need for high-resolution imaging and sophisticated analysis techniques, and the standardization of QSM acquisition and analysis protocols. Further research is necessary to refine QSM techniques, optimize acquisition parameters, and develop robust analysis pipelines to improve the sensitivity and specificity of detecting the diamagnetic nature of Aβ and τ aggregates. As our understanding of the diamagnetic properties of Aβ and τ continues to evolve, QSM is expected to play a pivotal role in advancing our knowledge of AD and other neurodegenerative diseases.