Plasma phosphorylated-tau181 levels reflect white matter microstructural changes across Alzheimer's disease progression.

Alzheimer's Disease (AD) is characterized by cognitive impairments that hinder daily activities and lead to personal and behavioral problems. Plasma hyperphosphorylated tau protein at threonine 181 (p-tau181) has recently emerged as a new sensitive tool for the diagnosis of AD patients. We herein investigated the association of plasma P-tau181 and white matter (WM) microstructural changes in AD. We obtained data from a large prospective cohort of elderly individuals participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI), which included baseline measurements of plasma P-tau181 and imaging findings. A subset of 41 patients with AD, 119 patients with mild cognitive impairments (MCI), and 43 healthy controls (HC) was included in the study, all of whom had baseline blood P-tau181 levels and had also undergone Diffusion Tensor Imaging. The analysis revealed that the plasma level of P-tau181 has a positive correlation with changes in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AxD), but a negative with Fractional Anisotropy (FA) parameters in WM regions of all participants. There is also a significant association between WM microstructural changes in different regions and P-tau181 plasma measurements within each MCI, HC, and AD group. In conclusion, our findings clarified that plasma P-tau181 levels are associated with changes in WM integrity in AD. P-tau181 could improve the accuracy of diagnostic procedures and support the application of blood-based biomarkers to diagnose WM neurodegeneration. Longitudinal clinical studies are also needed to demonstrate the efficacy of the P-tau181 biomarker and predict its role in structural changes.