Microstructural alterations of regional white matter tracts predict tau deposition in the Alzheimer’s disease signature regions

Abstract

AbstractBackgroundWe first aimed to investigate the association between regional white matter (WM) microstructural alterations with tau deposition in Alzheimer’s disease (AD) signature cortical regions. We also tried to develop models to predict pathological tau deposition positivity with regional WM microstructural alterations.MethodOne‐hundred nine older adults with normal cognition or mild cognitive impairment recruited from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer’s disease (KBASE) cohort were included in the analyses. All Participants underwent structural MRI (T1), diffusion tensor imaging, PiB‐PET and Tau‐PET (AV‐1451) scans. AD signature cortical regions for tau deposition included the angular gyrus, posterior cingulate, and inferior temporal cortical regions (Jack et al. 2017). Pathological tau positivity was determined by the presence of significantly high deposition in the Braak regions III‐VI according to the ADNI cutoff (Baker et al. 2017).ResultMean diffusivity (MD) of the posterior corona radiata, fornix, and posterior thalamic radiation were significantly associated with tau deposition in AD signature regions (F(1,107) = 13.48, p < 0.005; F(1,107) = 17.38, p < 0.001; F(1,107) = 15.92, p < 0.001, respectively) (Fig 1). Fractional anisotropy (FA) of the bilateral posterior thalamic radiation was also significantly associated with tau deposition in AD signature regions (F(1,107) = 17.14, p < 0.005) (Fig 1). Pathological tau positivity prediction model based on FA value of the posterior thalamic radiation, MD values of the posterior corona radiata and fornix had area under the curve (AUC) of receiver operating characteristics curve of 0.73 [0.62‐0.84] (Fig. 2a). With additional information on amyloid beta positivity, the AUC increased to 0.86 [0.78‐0.95] (Fig. 2b).ConclusionThe findings indicate that microstructural alterations of the specific regional WM tracts closely linked to AD‐signature cortical regions are strongly correlated with tau deposition in the same cortical regions. Moreover, the findings also support propagation of tauopathy through WM tracts. The information on regional WM alteration may be used for the prediction of pathological tau deposition.