Periventricular diffusion gradient of normal-appearing white matter and its transcriptional signatures in normal aging and multiple neurological diseases

Abstract Abnormal periventricular gradient of normal-appearing white matter (NAWM) is a common WM signature of aging and multiple neurological diseases. Here, we investigated the periventricular gradient of NAWM and its association with brain-wide gene expression in middle-aged and elderly participants with Alzheimer's disease, Parkinson's disease, cerebral small vessel disease, and multiple sclerosis compared to young healthy controls (HC), using diffusion magnetic resonance imaging data. Using the normalized neurite density and orientation dispersion indices, we observed the abnormal periventricular diffusion gradients in elderly HC and those with diseases, and the gradients correlated with brain volumes and cognitive performances. Using gene expression data, we observed the periventricular diffusion gradient in a normal aging population and patients with multiple neurological disorders associated with transcriptional changes in endothelial, synaptic, and immunologic functions. We determined a periventricular diffusion gradient of NAWM in normal aging and multiple neurological diseases and revealed its possible transcriptional signatures.