Effects of Amyloid Beta Peptide on Neurovascular Cells

Sholpan Askarova, Andrey Tsoy, Tamara Shalakhmetova, James C-M Lee

Abstract


Alzheimer’s disease (AD) is a chronic neurodegenerative disorder, which is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in specific regions of the brain, accompanied by impairment of the neurons, and progressive deterioration of cognition and memory of affected individuals. Although the cause and progression of AD are still not well understood, the amyloid hypothesis is dominant and widely accepted. According to this hypothesis, an increased deposition of amyloid-β peptide (Aβ) in the brain is the main cause of the AD’s onset and progression. There is increasing body of evidence that blood-brain barrier (BBB) dysfunction plays an important role in the development of AD, and may even precede neuron degeneration in AD brain. In the early stage of AD, microvasculature deficiencies, inflammatory reactions, surrounding the cerebral vasculature and endothelial dysfunctions are commonly observed. Continuous neurovascular degeneration and accumulation of Aβ on blood vessels resulting in cerebral amyloid angiopathy is associated with further progression of the disease and cognitive decline. However, little is known about molecular mechanisms that underlie Aβ induced damage of neurovascular cells. In this regards, this review is aimed to address how Aβ impacts the cerebral endothelium.  Understanding the cellular pathways triggered by Aβ leading to alterations in cerebral endothelial cells structure and functions would provide insights into the mechanism of BBB dysfunction and inflammatory processes in Alzheimer’s, and may offer new approaches for prevention and treatment strategies for AD.

 


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Kandel ER, Schwartz JH, Jessel TM, editors. Principles of Neural Science 4ed2000.

Hardy J, Selkoe DJ. The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics. Science. 2002;297(5580):353-6.

Vassar R. BACE1: the beta-secretase enzyme in Alzheimer's disease. J Mol Neurosci. 2004;23(1-2):105-14. Epub 2004/05/06.

Bernstein SL, Wyttenbach T, Baumketner A, Shea J-E, Bitan G, Teplow DB, et al. Amyloid β-Protein:  Monomer Structure and Early Aggregation States of Aβ42 and Its Pro19 Alloform. Journal of the American Chemical Society. 2005;127(7):2075-84.

Walsh DM, Selkoe DJ. Aβ Oligomers – a decade of discovery. Journal of Neurochemistry. 2007;101(5):1172-84.

Dahlgren KN, Manelli AM, Stine WB, Baker LK, Krafft GA, LaDu MJ. Oligomeric and Fibrillar Species of Amyloid-ОІ Peptides Differentially Affect Neuronal Viability. Journal of Biological Chemistry. 2002;277(35):32046-53.

Resende R, Ferreiro E, Pereira C, Resende de Oliveira C. Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1-42: Involvement of endoplasmic reticulum calcium release in oligomer-induced cell death. Neuroscience. 2008;155(3):725-37.

Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, et al. Natural oligomers of the amyloid-[beta] protein specifically disrupt cognitive function. Nat Neurosci. 2005;8(1):79-84.

Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci. 2011;12(12):723-38.

Stanimirovic DB, Friedman A. Pathophysiology of the neurovascular unit: disease cause or consequence[quest]. J Cereb Blood Flow Metab. 2011;32(7):1207-21.

Iadecola C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol 2010 120(3):287-96.

Liu R, Zhang T-t, Wu C-x, Lan X, Du G-h. Targeting the neurovascular unit: Development of a new model and consideration for novel strategy for Alzheimer's disease. Brain Research Bulletin. 2011;86(1–2):13-21.

Salmina A, Inzhutova A, Malinovskaya N, Petrova M. Endothelial dysfunction and repair in Alzheimer-type neurodegeneration: neuronal and glial control. J Alzheimers Dis. 2010;22(1):17-36.

Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, et al. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol. 2005;57(6):789-94. Epub 2005/06/02.

Zlokovic BV. New therapeutic targets in the neurovascular pathway in Alzheimer's disease. Neurotherapeutics. 2008;5(3):409-14. Epub 2008/07/16.

Bell R, Zlokovic B. Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease. Acta Neuropathologica. 2009;118(1):103-13.

Iadecola C. Cerebrovascular effects of amyloid-beta peptides: mechanisms and implications for Alzheimer's dementia. Cell Mol Neurobiol. 2003;23(4-5):681-9.

de la Torre JC. How do heart disease and stroke become risk factors for Alzheimer's disease? Neurological Research. 2006;28:637-44.

Deane R, Zlokovic BV. Role of the Blood-Brain Barrier in the pathogenesis of Alzheimers disease. Current Alzheimer Research 2007(4):191-7.

Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol. 2006;100(1):328-35.

Hofman A, Ott A, Breteler MMB, Bots ML, Slooter AJC, van Harskamp F, et al. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. The Lancet. 1997;349(9046):151-4.

Bradbury MW. The blood-brain barrier. Transport across the cerebral endothelium. Circ Res. 1985;57(2):213-22.

Scheibel A, Duong T, Jacobs R. Alzheimer's disease as a capillary dementia. Ann Med. 1989;21(2):103-7.

De la Torre JC. Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. The Lancet Neurology. 2004;3(3):184-90.

Borroni B, Akkawi N, Martini G, Colciaghi F, Prometti P, Rozzini L, et al. Microvascular damage and platelet abnormalities in early Alzheimer's disease. Journal of the Neurological Sciences. 2002;203-204:189-93.

Farkas E, Luiten PGM. Cerebral microvascular pathology in aging and Alzheimer's disease. Progress in Neurobiology. 2001;64(6):575-611.

Luc B, Patrick R HOF, AndrЙ D. Brain Microvascular Changes in Alzheimer's Disease and Other Dementiasa. Annals of the New York Academy of Sciences. 1997;826(Cerebrovascular Pathology in Alzheimer's Disease):7-24.

Berzin TM, Zipser BD, Rafii MS, Kuo--Leblanc V, Yancopoulos GD, Glass DJ, et al. Agrin and microvascular damage in Alzheimer's disease. Neurobiology of Aging. 2000;21(2):349-55.

Bailey TL, Rivara CB, Rocher AB, Hof PR. The nature and effects of cortical microvascular pathology in aging and Alzheimer's disease. Neurological Research. 2004;26:573-8.

Kalaria RN, Pax AB. Increased collagen content of cerebral microvessels in Alzheimer's disease. Brain Research. 1995;705(1-2):349-52.

Ervin JF, Pannell C, Szymanski M, Welsh-Bohmer K, Schmechel DE, Hulette CM. Vascular Smooth Muscle Actin Is Reduced in Alzheimer Disease Brain: A Quantitative Analysis. Journal of Neuropathology & Experimental Neurology. 2004;63(7):735-41.

Kalaria RN HP. Differential degeneration of the cerebral microvasculature in Alzheimer’s disease. Neuroreport. 1995(6):477-80.

Claudio L. Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients. Acta Neuropathologica 1996; 91(1):6-14.

Aliev G, Seyidova D, Lamb BT, Obrenovich ME, Siedlak SL, Vinters HV, et al. Mitochondria and vascular lesions as a central target for the development of Alzheimer's disease and Alzheimer disease-like pathology in transgenic mice. Neurological Research. 2003;25:665-74.

Magrane J, Christensen RA, Rosen KM, Veereshwarayya V, Querfurth HW. Dissociation of ERK and Akt signaling in endothelial cell angiogenic responses to [beta]-amyloid. Experimental Cell Research. 2006;312(7):996-1010.

Hayashi S-i, Sato N, Yamamoto A, Ikegame Y, Nakashima S, Ogihara T, et al. Alzheimer Disease-Associated Peptide, Amyloid {beta}40, Inhibits Vascular Regeneration With Induction of Endothelial Autophagy. Arterioscler Thromb Vasc Biol. 2009;29(11):1909-15.

Price JM, Chi X, Hellermann G, Sutton ET. Physiological levels of -amyloid induce cerebral vessel dysfunction and reduce endothelial nitric oxide production. Neurological Research. 2001;23:506-12.

Emmanuelle MB, Michal T, Robert JM, Bernhard H. Amyloid β-Peptide Induces Cell Monolayer Albumin Permeability, Impairs Glucose Transport, and Induces Apoptosis in Vascular Endothelial Cells. Journal of Neurochemistry. 1997;68(5):1870-81.

Bhatia R, Lin HAI, Lal R. Fresh and globular amyloid {beta} protein (1-42) induces rapid cellular degeneration: evidence for A{beta}P channel-mediated cellular toxicity. FASEB J. 2000;14(9):1233-43.

Xu J, Chen S, Ku G, Ahmed SH, Xu J, Chen H, et al. Amyloid beta Peptide-Induced Cerebral Endothelial Cell Death Involves Mitochondrial Dysfunction and Caspase Activation. J Cereb Blood Flow Metab. 2001;21(6):702-10.

Selkoe DJaS, D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol. 2003;(43):545-84.

Kalaria RN. Cerebrovascular Degeneration Is Related to Amyloid-β Protein Deposition in Alzheimer's Disease. Annals of the New York Academy of Sciences. 2006;826(Issue Cerebrovascular Pathology in Alzheimer's Disease):263-71.

Park L AJ, Forster C, Kazama K, Carlson GA, Iadecola C. Abeta-induced vascular oxidative stress and attenuation of functional hyperemia in mouse somatosensory cortex. Joyrnal of Cerebral Blood Flow Metabolism. 2004;24(3):334-42.

Iadecola C ZF, Niwa K, Eckman C, Turner SK, Fischer E, Younkin S, Borchelt DR, Hsiao KK, Carlson GA. SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nature Neuroscience. 1999;2(2):157-61.

Tong X-K, Nicolakakis N, Kocharyan A, Hamel E. Vascular Remodeling versus Amyloid-beta-Induced Oxidative Stress in the Cerebrovascular Dysfunctions Associated with Alzheimer's Disease. J Neurosci. 2005;25(48):11165-74.

Abramov AY, Duchen MR. The role of an astrocytic NADPH oxidase in the neurotoxicity of amyloid beta peptides. Philosophical Transactions of the Royal Society B: Biological Sciences. 2005;360(1464):2309-14.

Yin KJ, Lee JM, Chen SD, Xu J, Hsu CY. Amyloid-beta Induces Smac Release via AP-1/Bim Activation in Cerebral Endothelial Cells. J Neurosci. 2002;22(22):9764-70.

Hsu M-J, Hsu CY, Chen B-C, Chen M-C, Ou G, Lin C-H. Apoptosis Signal-Regulating Kinase 1 in Amyloid {beta} Peptide-Induced Cerebral Endothelial Cell Apoptosis. J Neurosci. 2007;27(21):5719-29.

Grammas P, Ovase R. Inflammatory factors are elevated in brain microvessels in Alzheimer's disease. Neurobiology of Aging. 2001;22(6):837-42.

Vukic V, Callaghan D, Walker D, Lue L-F, Liu QY, Couraud P-O, et al. Expression of inflammatory genes induced by beta-amyloid peptides in human brain endothelial cells and in Alzheimer's brain is mediated by the JNK-AP1 signaling pathway. Neurobiology of Disease. 2009;34(1):95-106.

Tan J, Town T, Suo Z, Wu Y, Song S, Kundtz A, et al. Induction of CD40 on human endothelial cells by Alzheimer's [beta]-amyloid peptides. Brain Research Bulletin. 1999;50(2):143-8.

Suo Z, Tan J, Placzek A, Crawford F, Fang C, Mullan M. Alzheimer's [beta]-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40. Brain Research. 1998;807(1-2):110-7.

Callaghan D, Bai J, Huang A, Vukic V, Xiong H, Jones A, et al. P4-182: Inhibition of ABCG2 transport function by amyloid-beta peptide augments cellular oxidative stress and inflammatory gene expression in cells. Alzheimer's and Dementia. 2008;4(4, Supplement 1):T724-T.

Park L, Anrather J, Zhou P, Frys K, Pitstick R, Younkin S, et al. NADPH Oxidase-Derived Reactive Oxygen Species Mediate the Cerebrovascular Dysfunction Induced by the Amyloid {beta} Peptide. J Neurosci. 2005;25(7):1769-77.

Park L, Zhou P, Pitstick R, Capone C, Anrather J, Norris EH, et al. Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Proceedings of the National Academy of Sciences. 2008;105(4):1347-52.

Cai H, Griendling KK, Harrison DG. The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends in Pharmacological Sciences. 2003;24(9):471-8.

Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, et al. RAGE and amyloid-[beta] peptide neurotoxicity in Alzheimer's disease. Nature. 1996;382(6593):685-91.

Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, Puzzo D, et al. RAGE potentiates A[beta]-induced perturbation of neuronal function in transgenic mice. EMBO J. 2004;23(20):4096-105.

Chaney MO, Stine WB, Kokjohn TA, Kuo Y-M, Esh C, Rahman A, et al. RAGE and amyloid beta interactions: Atomic force microscopy and molecular modeling. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2005;1741(1-2):199-205.

Sasaki N, Toki S, Chowei H, Saito T, Nakano N, Hayashi Y, et al. Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease. Brain Research. 2001;888(2):256-62.

Lue L-F, Walker DG, Brachova L, Beach TG, Rogers J, Schmidt AM, et al. Involvement of Microglial Receptor for Advanced Glycation Endproducts (RAGE) in Alzheimer's Disease: Identification of a Cellular Activation Mechanism. Experimental Neurology. 2001;171(1):29-45.

Askarova S, Yang X, Sheng W, Sun GY, Lee JC-M. Role of Ab-Receptor for advanced endproducts in oxidativestress and cytosolic phospholipase A2 activation in astrocytes and cerebral endothelial cells. Neuroscience. 2011;199:375-85.

Wautier M-P, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier J-L. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab. 2001;280(5):E685-94.

Giri R, Shen Y, Stins M, Du Yan S, Schmidt AM, Stern D, et al. Beta-amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. Am J Physiol Cell Physiol. 2000;279(6):C1772-81.

Takuma K, Fang F, Zhang W, Yan S, Fukuzaki E, Du H, et al. RAGE-mediated signaling contributes to intraneuronal transport of amyloid-ОІ and neuronal dysfunction. Proceedings of the National Academy of Sciences. 2009;106(47):20021-6.

Zhu D, Lai Y, Shelat PB, Hu C, Sun GY, Lee JCM. Phospholipases A2 Mediate Amyloid-beta Peptide-Induced Mitochondrial Dysfunction. J Neurosci. 2006;26(43):11111-9.

Stephenson DT, Lemere CA, Selkoe DJ, Clemens JA. Cytosolic phospholipase A2 (cPLA2) immunoreactivity is elevated in Alzheimer's disease brain. Neurobiol Dis. 1996;3(1):51-63. Epub 1996/02/01.

Moses GS, Jensen MD, Lue LF, Walker DG, Sun AY, Simonyi A, et al. Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease. J Neuroinflammation. 2006;3:28. Epub 2006/10/10.

Dineley KT, Westerman M, Bui D, Bell K, Ashe KH, Sweatt JD. {beta}-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal {alpha}7 Nicotinic Acetylcholine Receptors: In Vitro and In Vivo Mechanisms Related to Alzheimer's Disease. J Neurosci. 2001;21(12):4125-33.

Young KF, Pasternak SH, Rylett RJ. Oligomeric aggregates of amyloid [beta] peptide 1-42 activate ERK/MAPK in SH-SY5Y cells via the [alpha]7 nicotinic receptor. Neurochemistry International. 2009;55(8):796-801.

McDonald DR, Bamberger ME, Combs CK, Landreth GE. beta -Amyloid Fibrils Activate Parallel Mitogen-Activated Protein Kinase Pathways in Microglia and THP1 Monocytes. J Neurosci. 1998;18(12):4451-60.

Shelat P, B. , Chalimoniuk M, Wang J-H, Strosznajder J, B. , Lee J, C. , Sun A, Y. , et al. Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. Journal of Neurochemistry. 2008;106(1):45-55.

Stephenson D, Rash K, Smalstig B, Roberts E, Johnstone E, Sharp J, et al. Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration. Glia. 1999;27(2):110-28. Epub 1999/07/27.

Sun GY, Horrocks LA, Farooqui AA. The roles of NADPH oxidase and phospholipases A2 in oxidative and inflammatory responses in neurodegenerative diseases. Journal of Neurochemistry. 2007;103(1):1-16.

Maat-Schieman ML vDS, Rozemuller AJ, Haan J, Roos RA. Association of vascular amyloid beta and cells of the mononuclear phagocyte system in hereditary cerebral hemorrhage with amyloidosis (Dutch) and Alzheimer disease. J Neuropathol Exp Neurol. 1997(56):273-84.

Uchihara T AH, Kondo H, Ikeda K. Activated microglial cells are colocalized with perivascular deposits of amyloid-beta protein in Alzheimer's disease brain. Stroke. 1997(28):1948-50.

Selkoe DJ, Schenk D. ALZHEIMER'S DISEASE: Molecular Understanding Predicts Amyloid-Based Therapeutics. Annual Review of Pharmacology and Toxicology. 2003;43(1):545-84.

Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR. Turning Blood into Brain: Cells Bearing Neuronal Antigens Generated in Vivo from Bone Marrow. Science. 2000;290(5497):1779-82.

Giri R, Selvaraj S, Miller CA, Hofman F, Yan SD, Stern D, et al. Effect of endothelial cell polarity on beta -amyloid-induced migration of monocytes across normal and AD endothelium. Am J Physiol Cell Physiol. 2002;283(3):C895-904.

Reyes Barcelo A, Gonzalez-Velasquez F, Moss M. Soluble aggregates of the amyloid-beta peptide are trapped by serum albumin to enhance amyloid-beta activation of endothelial cells. Journal of Biological Engineering. 2009;3(1):5.

Gonzalez-Velasquez FJ, Kotarek JA, Moss MA. Soluble aggregates of the amyloid-beta protein selectively stimulate permeability in human brain microvascular endothelial monolayers. J Neurochem. 2008;107:466-77.

Frijns CJ, Kappelle LJ. Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke. 2002;33(8):2115-22.

Alon R, Chen S, Puri KD, Finger EB, Springer TA. The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling. J Cell Biol. 1997;138(5):1169-80.

Alon R, Hammer DA, Springer TA. Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature. 1995;374(6522):539-42.

Dembo M, Torney DC, Saxman K, Hammer D. The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proc R Soc Lond B Biol Sci. 1988;234(1274):55-83.

Trache A, Trzeciakowski JP, Gardiner L, Sun Z, Muthuchamy M, Guo M, et al. Histamine effects on endothelial cell fibronectin interaction studied by atomic force microscopy. Biophys J. 2005;89(4):2888-98.

Sun M, Northup N, Marga F, Huber T, Byfield FJ, Levitan I, et al. The effect of cellular cholesterol on membrane-cytoskeleton adhesion. J Cell Sci. 2007;120(13):2223-31.

Sun M, Graham JS, Hegedьs B, Marga F, Zhang Y, Forgacs G, et al. Multiple Membrane Tethers Probed by Atomic Force Microscopy. 2005;89(6):4320-9.

Girdhar G, Shao J-Y. Membrane Tether Extraction from Human Umbilical Vein Endothelial Cells and Its Implication in Leukocyte Rolling. Biophysical Journal. 2004;87(5):3561-8.

Girdhar G, Chen Y, Shao J-Y. Double-Tether Extraction from Human Umbilical Vein and Dermal Microvascular Endothelial Cells. Biophysical Journal. 2007;92(3):1035-45.

Lee JCM, Askarova S, Sun Z, Sun GY, Meininger GA. P4-293: Oligomeric amyloid-ОІ peptide on sialyl LewisX-selectin bonding at the cerebral endothelial cell surface. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2008;4(4):T757.

Bednarczyk J, Lukasiuk K. Tight junctions in neurological diseases. Acta Neurobiol Exp. 2011;71(4):393-408.

Chen X, Gawryluk J, Wagener J, Ghribi O, Geiger J. Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease. Journal of Neuroinflammation. 2008;5(1):12.

Marco S, Skaper SD. Amyloid [beta]-peptide1-42 alters tight junction protein distribution and expression in brain microvessel endothelial cells. Neuroscience Letters. 2006;401(3):219-24.

Nishitsuji K, Hosono T, Nakamura T, Bu G, M. M. Apolipoprotein E regulates the integrity of tight junctions in an isoform-dependent manner in an in vitro blood-brain barrier model. J Biol Chem. 2011;286(20):17536-4.

Omolola Eniola A, Hammer DA. In vitro characterization of leukocyte mimetic for targeting therapeutics to the endothelium using two receptors. Biomaterials. 2005;26(34):7136-44.




DOI: https://doi.org/10.5195/cajgh.2012.4

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