Table 1. Potential causes and consequences of proposed BBB dysfunction in AD.

BBB dysfunction		Upstream causes		Downstream consequences
Disruption		Aβ oligomers, truncated tau, inflammation, oxidative stress, diabetes, ApoE4 allele, TBI, vascular disease		Leakage of serum components into CNS, neurotoxicity, inflammatory activation
Altered transport	Of Aβ	↓LRP-1	Aβ oligomers, inflammation, oxidative stress, diabetes	Aβ accumulation in the CNS
		↓Pgp	Aβ oligomers, inflammation, TBI	Aβ accumulation in the CNS, altered xenobiotic transport
		↑RAGE	Aβ oligomers, diabetes, inflammation, oxidative stress	Aβ accumulation in the CNS, vascular inflammation
	Of glucose	↓GLUT-1	Aβ oligomers, ApoE4 allele	Energy deprivation, neuronal dysfunction
Altered secretions	Of thrombin	Oxidative stress, ischemia		Neurotoxicity, BBB disruption
	Of VEGF	Oxidative stress, ischemia		Neurotoxicity, BBB disruption, angiogenesis

Aβ, amyloid-β; AD, Alzheimer's disease; ApoE, Apolipoprotein E; BBB, blood–brain barrier; CNS, central nervous system; LRP-1, lipoprotein receptor-related protein-1; Pgp, P-glycoprotein; RAGE, receptor for advanced glycation endproducts; TBI, traumatic brain injury; VEGF, vascular endothelial growth factor.