Congratulations to Juan Pablo Palavicini, PhD and Xianlin Han, PhD on their recent publication in International Journal of Molecular Sciences!
Juan Pablo Palavicini, PhD is the co-first author and Xianlin Han, PhD is the corresponding author on the recently published paper in International Journal of Molecular Sciences. Dr. Palavicini is an Assistant Professor/Research and Dr. Han is a Professor, both with the Sam and Ann Barshop Institute for Longevity and Aging Studies and the Department of Medicine, Division of Diabetes in the Joe R. and Teresa Lozano Long School of Medicine.
Sulfatide Deficiency, an Early Alzheimer’s Lipidomic Signature, Causes Brain Ventricular Enlargement in the Absence of Classical Neuropathological Hallmarks
By: Juan Pablo Palavicini, Lin Ding, Meixia Pan, Shulan Qiu, Hu Wang, Qiang Shen, Jeffrey L. Dupree, and Xianlin Han
International Journal of Molecular Sciences, 2023, 24(1), 233; https://doi.org/10.3390/ijms24010233
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and a decline in activities of daily life. Ventricular enlargement has been associated with worse performance on global cognitive tests and AD. Our previous studies demonstrated that brain sulfatides, myelin-enriched lipids, are dramatically reduced in subjects at the earliest clinically recognizable AD stages via an apolipoprotein E (APOE)-dependent and isoform-specific process. Herein, we provided pre-clinical evidence that sulfatide deficiency is causally associated with brain ventricular enlargement. Specifically, taking advantage of genetic mouse models of global and adult-onset sulfatide deficiency, we demonstrated that sulfatide losses cause ventricular enlargement without significantly affecting hippocampal or whole brain volumes using histological and magnetic resonance imaging approaches. Mild decreases in sulfatide content and mild increases in ventricular areas were also observed in human APOE4 compared to APOE2 knock-in mice. Finally, we provided Western blot and immunofluorescence evidence that aquaporin-4, the most prevalent aquaporin channel in the central nervous system (CNS) that provides fast water transportation and regulates cerebrospinal fluid in the ventricles, is significantly increased under sulfatide-deficient conditions, while other major brain aquaporins (e.g., aquaporin-1) are not altered. In short, we unraveled a novel and causal association between sulfatide deficiency and ventricular enlargement. Finally, we propose putative mechanisms by which sulfatide deficiency may induce ventricular enlargement.
Keywords: sulfatide; cerebroside sulfotransferase; ventricular enlargement; Alzheimer’s disease; brain MRI; aquaporins