Haoyue
Zhou

Dr. Haoyue Zhou is a postdoctoral scholar at the Gladstone Institutes. During her graduate training in Dr. Yong Shen’s lab at the University of Science and Technology of China, she investigated the pathogenesis of cerebral small vessel disease (CSVD) and its contribution to Alzheimer’s disease (AD). Her research revealed that BACE1, best known for generating amyloid peptide in neurons, is also expressed in brain endothelial cells, where it drives CSVD. Integrating human patient samples with mouse and cell models, she identified occludin, a tight junction protein critical for blood-brain barrier (BBB) integrity, as a novel BACE1 substrate. Hypertension-driven BACE1 overexpression caused excessive occludin cleavage, disrupting BBB tight junctions and impairing nitric oxide signaling, ultimately producing cognitive impairment in mice. This work established a mechanistic link between vascular pathology and neurodegeneration. As a postdoctoral researcher in Dr. Andrew Yang’s lab at the Gladstone Institutes, she expanded her focus to body-brain communication across the BBB and its role in shaping AD pathology. She developed a platform integrating bioorthogonal labeling with mass spectrometry to achieve the first systematic mapping of plasma proteins that cross the intact BBB, uncovering novel periphery-to-brain signaling pathways. The most exciting candidate she identified was APOA1, a liver-derived lipoprotein that selectively homes to astrocytes, pointing to a direct liver-astrocyte signaling axis. Her ongoing work aims to define how APOA1 regulates astrocytic functions, including lipid metabolism and synaptic support, and how its transport across the BBB is altered in early-stage AD. These insights will establish a framework for understanding periphery-to-brain signaling in AD onset and inform the development of receptor-based shuttles for precise CNS drug delivery.