Alzheimer's & dementia (Amsterdam, Netherlands) · 2026
Associations of plasma phosphorylated tau217 with cognitive impairment and brain microstructural alterations in Alzheimer's disease.
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Rivas-Fernández Miguel Ángel, Basanta-Torres Sara, Lindín Mónica, Zurrón Montserrat, Díaz Fernando, Pereiro Arturo Xosé, Lojo-Seoane Cristina, Rodríguez-Pérez Ana Isabel, Labandeira José Luis, Galdo-Álvarez Santiago
Аннотация
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.
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.