Abstract
Alzheimer’s disease, a type of dementia, affects memory, behavior, and cognitive processes in affected individuals. It is one of the prominent diseases, accounting for 60–80% of dementia cases and affecting a significant population of persons over the age of 65 years. While rare, Alzheimer’s disease (AD) may affect the younger population as well. With such a widespread number of persons affected with AD, scientists have undertaken the initiative to develop a cure for this devastating disease; however, it has been deemed quite challenging. A dysfunctional blood-brain barrier, with impaired ability to clear amyloid-β from the brain, has been directly linked to the development of Alzheimer’s disease. The blood-brain barrier restricts the flow of many substances into and out of the brain and serves as a selective and protective barrier to the brain. A proper functioning blood-brain barrier contributes to the maintenance and integrity of the brain. In turn, different systems and mechanisms within the blood-brain barrier are set in place to facilitate mediated passage of materials and substances between the brain and the bloodstream. In relation to AD, the mediation of amyloid-β clearance is of great importance in maintaining the blood-brain barrier’s integrity.
Keywords
- Low-density Lipoprotein Receptor-related Protein (LRP1)
- Phosphatidylinositol-binding Clathrin Assembly (PICLAM)
- Apolipoprotein E Receptor 2 (ApoER2)
- Cerebral Amyloid Angiopathy (CAA)
- Kanekiyo
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Irsalan Cockerill and Joy-Anne Oliver are contributed equally to this work.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Aarts MM, Arundine M (2003) Novel concepts in excitotoxic neurodegeneration after stroke. Expert Rev Mol Med 5:1–22
Bhattacharjee S, Zhao Y, Hill JM, Culicchia F, Kruck TP, Percy ME et al (2013) Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD). J Inorg Biochem 126:35–37
Bhattacharjee S, Zhao Y, Hill JM, Percy ME, Lukiw WJ (2014) Aluminum and its potential contribution to Alzheimer's disease (AD). Front Aging Neurosci 6:1–3
Deane R, Bell RD, Sagare A, Zlokovic BV (2009, March) Clearance of Amyloid-β Peptide Across the Blood-Brain Barrier: Implication for Therapies in Alzheimer's Disease. CNS Neurol Disord Drug Targets 8:16–30
ElAli A, Rivest S (2013) The role of ABCB1 and ABCA1 in beta-amyloid clearance at the neurovascular unit in Alzheimer's disease. Frontierd in Aging Neuroscience; 1-6
Exley C, Price NC, Kelly SM, Birchall JD (1993) An interation of B-amyloid with aluminum in vitro. FEBS Lett 324:293–295
Gamba P, Testa G, Gargiulo S, Staurenghi E, Poli G, Leonarduzzi G (2015) Oxidized cholesterol as the criving force behind the development of Alzheimer's disease. Front Aging Neurosci 7:1–21
Gonzalez-Marrero I, Gimenez-Llort L, Johanson CE, Carmona-Calero EM, Castaneyra-Ruiz L, Brito-Armas JM et al (2015) Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic model of Alzheimer's disease. Front Cell Neurosci 9:1–10
Grimm MO, Grimm HS, Tomic I, Beyreuther K, Hartmann T, Bergmann C (2008) Independent Inhibition of Alzheimer's Disease β- and γ-Secretase Cleavage by Lowered Cholesterol Levels. J Biol Chem 283: 11302–11311
Haorah J, Ramirez SH, Schall K, Smith D, Pandya RP (2007) Oxidative stress activates protein tyrosine kinsase and matrix metalloproteinases leading to blood-brain barrier dysfunction. J Neurochem 101:566–576
Joan Abbott N, Friedman A (2013) Overview and introduction: The blood–brain barrier in health and disease. Epilepsia 53:1–6
Kanekiyo T, Bu G (2014) The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer's disease. Front Aging Neurosci 6:1–12
Kawahara M, Kato-Negishi M (2011) Link between Aluminum and the Pathogenesis of Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade Hypothesis. Int J Alzheimers Dis 2011:1–17
Kreutzer JS, DeLuca J, Caplan B (2011) Blood brain barrier. In: Tran N (ed) Encyclopedia of clinical neuropsychology. Springer, New York, p 426
Liu YC (2012) Modern methods for delivery of drugs across the blood–brain barrier. Adv Drug Deliv Rev 64:640–665
Lun MP, Monuki ES, Lehtinen MK (2016) Development and functions of the choroid plexus-cerebrospinal fluid system. Nat Reviews 16:445–457
Mirza A, King A, Troakes C, Exley C (2017) Aluminum in brain tissue in familial Alzheimer's disease. J Trace Elem Med Biol 40:30–36
Mullins RJ, Diehl TC, Chia CW, Kapogiannis D (2017) Insulin resistance as a link between amyloid-beta and tau pathologies in Alzheimer's disease. Front Aging Neurosci 9:1–16
Ramanathan A, Nelson AR, Sagare AP, Zlokovic BV (2015) Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer's disease: the role, regulation and restoration of LRP1. Front Aging Neurosci 7:1–12
Tajes M, Ramos-Fernandez E, Weng-Jiang X, Bosch-Morato M, Guivernau B, Eraso-Pichot A et al (2014) The blood-brain barrier: Structure, function and therapeutic approaches. Mol Membr Biol 31:152–167
Talbot K, Wang H-Y, Kazi H, Han L-Y, Bakshi KP, Stucky A et al (2012) Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 122:1316–1338
Weiss N, Miller F, Cazaubon S (2009) The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 1788:843–852
Wolburg UK (2000) Tight junctions of the blood–brain barrier. Cell Mol Neurobiol 20:57–76
Zenaro E, Piacentino G, Constantin G (2016) The blood-brain barrier in Alzheimer's disease. Neuobiol Dis 107:1–16
Zhagi J, Goldenson B, Inayathullah M, Lossinsky AS, Masoumi A, Avagyan H et al (2009) Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy. Acta Neuropathol 117:111–124
Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV (2015a) Establishment and dysfunction of the blood-brain barrier. Cell 163:1064–1078
Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K et al (2015b) Central role for PICLAM in amyloid-β blood-brain barrier transcytosis and clearance. Nat Neurosci 18:978–987
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Cockerill, I., Oliver, JA., Xu, H., Fu, B.M., Zhu, D. (2018). Blood-Brain Barrier Integrity and Clearance of Amyloid-β from the BBB. In: Fu, B., Wright, N. (eds) Molecular, Cellular, and Tissue Engineering of the Vascular System. Advances in Experimental Medicine and Biology, vol 1097. Springer, Cham. https://doi.org/10.1007/978-3-319-96445-4_14
Download citation
DOI: https://doi.org/10.1007/978-3-319-96445-4_14
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-96444-7
Online ISBN: 978-3-319-96445-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)