Blood–Brain Barrier Degradation and the Implication of SPARC Protein as a Potential Therapeutic Target for Alzheimer’s Disease

ABSTRACT Alzheimer’s disease is a progressive neurodegenerative disorder affecting a substantial portion of the older population, with the number of afflicted individuals expected to grow with time. Although numerous contributing factors to the disorder have been identified, there is currently no cure or effective prevention method. With the situation as dire as it is, many efforts have been made to shed light on the mechanisms tying diverse contributing factors to the pathogenesis of Alzheimer’s disease. One common neuropathological feature of Alzheimer’s disease is the dysfunction of the blood–brain barrier, which normally maintains brain homeostasis by isolating it from the peripheral circulation and mediating the transport of various bloodborne elements in and out of the brain. An increase in the blood–brain barrier permeability has been observed in Alzheimer’s disease at a level considerably above normal aging. This chapter provides an overview of the effects of aging, the neuroimmune system, inflammation, traumatic brain injury, apolipoprotein E gene e4 allele, and secreted protein acidic and rich in cysteine (SPARC) protein on blood–brain barrier. The potential of SPARC as a therapeutic target for Alzheimer’s disease, and the application of deep-learning-based virtual screening tools against SPARC protein are explored.