Coba Lab

University of Southern California

PHYSIOLOGY

Los Angeles · United States

NIH-funded
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NIH R01 · 2025

PICALM: Role in the pathogenesis and treatment of Alzheimer vascular blood-brain barrier clearance dysfunction, neuronal dysfunction, and amyloid-beta, tau and neurodegenerative disorders

PICALM is one of the most significant susceptibility factors for late onset Alzheimer’s disease (LOAD). Its role in disease pathogenesis, however, remains elusive. We also do not have an effective PICALM-based therapy for AD. PICALM controls internalization of cell receptors, and intracellular trafficking of different proteins. PICALM is abundantly expressed in brain endothelium and neurons, but is reduced in LOAD and by some PICALM SNPs. To understand how PICALM regulates vascular and neuronal function and AD pathology, we developed new mouse models with PICALM-specific deletion from endothelium and neurons. The proposed studies are supported by our pilot data showing: i) that PICALM…

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