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 ε4 allele, and secreted protein acidic and rich in cysteine (SPARC) protein on blood-brain barrier. The potential

Blood–Brain Barrier Breakdown: An Emerging Biomarker of Cognitive Impairment in Normal Aging and Dementia

“…In addition, secreted protein acidic and rich in cysteine (SPARC) was identified to decrease transendothelial electrical resistance (TEER) and TJ proteins (ZO-1, OCLN) and increase paracellular permeability by regulating the tyrosine kinase pathway (Alkabie et al, 2016 ). Hence, the SPARC–collagen binding domain might be a potential therapeutic target to treat AD (Pilozzi et al, 2020 ). Furthermore, SPARC/Hevin normalization may also be considered as a novel therapeutic target for the modulation of AD progression (Strunz et al, 2019 ).…”

Longitudinal markers of cerebral amyloid angiopathy and related inflammation in rTg-DI rats

“…10 ). SPARC has been suggested as a key initiator of cerebral inflammation in AD and BBB permeability as well, thus may be another CAA-ri marker 76 .…”

Biological Significance of the Protein Changes Occurring in the Cerebrospinal Fluid of Alzheimer’s Disease Patients: Getting Clues from Proteomic Studies

“…Based on our results, four members of this family are differently altered in AD CSF. This family of proteins comprises six members that present calcium-binding domains and regulate cell interaction with the microenvironment [ 89 ]. It is worth highlighting the potential role of SPRC on vascular pathology in AD.…”

“…It is worth highlighting the potential role of SPRC on vascular pathology in AD. In the brain, SPRC is also expressed in endothelial cells, wherein it affects trans-endothelial permeability [ 89 ]. Moreover, since it acts as a chaperone of collagen IV through the SPRC-collagen binding domain, it has been observed a direct relationship between increased SPRC, collagen IV, and the thickening of the basal lamina of the cerebral vasculature, a feature commonly observed in AD brains [ 89 , 90 , 91 ].…”