Associations of plasma phosphorylated tau217 with cognitive impairment and brain microstructural alterations in Alzheimer's disease.

INTRODUCTION

Plasma phosphorylated tau217 (p-tau217) is a promising biomarker for Alzheimer's disease (AD) risk detection. Its relationship with brain microstructure and cognitive impairment remains unclear. Multi-component T2-relaxometry is an MRI technique sensitive to myelin content, axonal degeneration, and neuroinflammation.

METHODS

A total of 229 participants classified by p-tau217 levels into p-tau217- (n = 176), p-tau217+ (n = 26), and intermediate (n = 27) underwent neuropsychological testing and MRI. Voxel-wise general linear models controlling for age, sex, education, apolipoprotein E (APOE, and white matter lesions were performed for total water content (TWC), myelin water fraction (MWF), intra-/extracellular water fraction (IEWF), geometric mean of intra-/extracellular water (T2IE), and free/quasi-free water fraction (FQFWF).

RESULTS

The p-tau217+ participants showed poorer cognition, increases in FQFWF and TWC, and reductions in IEWF and T2IE across cortical and subcortical regions and white matter tracts.

DISCUSSION: High p-tau217 level associates with brain microstructure alterations and poorer cognition, supporting it as a biomarker of AD-related neuropathology and the utility of T2-relaxometry for detecting tissue integrity.