Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease

Journal of Cerebral Blood Flow and Metabolism

Volumn 33, Issue 10, 2013, Pages 1500-1513

  Erickson, Michelle A ^a,b,c   Banks, William A ^a,b  

^a VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Alzheimer's disease; blood brain barrier; cerebrospinal fluid; diabetes; inflammation; neurovascular unit

Indexed keywords

ALBUMIN; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E2; APOLIPOPROTEIN E3; APOLIPOPROTEIN E4; BREAST CANCER RESISTANCE PROTEIN; CLAUDIN 5; COMPLEMENT COMPONENT C1Q; COMPLEMENT COMPONENT C3C; CREATININE; GLUCOSE TRANSPORTER 1; HEMOGLOBIN; HEMOSIDERIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; PHOSPHOLIPASE A2; PREALBUMIN; SERUM AMYLOID P; TAU PROTEIN;

AGING; ALBUMIN BLOOD LEVEL; ALLELE; ALZHEIMER DISEASE; ASTROCYTE; BINDING AFFINITY; BLOOD BRAIN BARRIER; BRAIN ATROPHY; BRAIN ISCHEMIA; CARDIOVASCULAR RISK; CELL CONTACT; CEREBROSPINAL FLUID; CEREBROVASCULAR ACCIDENT; COMPUTER ASSISTED TOMOGRAPHY; CREATININE BLOOD LEVEL; DIFFUSE LEWY BODY DISEASE; ENDOCYTOSIS; EXTRACELLULAR MATRIX; HUMAN; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; INTERSTITIAL FLUID; INTRACRANIAL PRESSURE; MAJOR DEPRESSION; METABOLIC SYNDROME X; MICROGLIA; MULTIINFARCT DEMENTIA; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NEUROIMAGING; NEUROTOXICITY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUTRIENT SUPPLY; OBESITY; OXIDATIVE STRESS; PERICYTE; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAGE; REVIEW; RISK FACTOR; TIGHT JUNCTION; TRAUMATIC BRAIN INJURY; VASCULAR AMYLOIDOSIS;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; EXCITATORY AMINO ACID TRANSPORTER 2; HUMANS; OXIDATIVE STRESS; RISK FACTORS; SERUM ALBUMIN;

EID: 84885018413     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2013.135     Document Type: Review

References (238)

1. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992; 256: 184-185.
2. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-356. (Pubitemid 34790756)
3. Saido T, Leissring MA. Proteolytic degradation of amyloid beta-protein. Cold Spring Harb Perspect Med 2012; 2: a006379.
4. Johanson CE, Duncan 3rd JA, Klinge PM, Brinker T, Stopa EG, Silverberg GD. Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res 2008; 5: 10.
5. Zlokovic BV. Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci 2005; 28: 202-208. (Pubitemid 40445527)
6. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37: 13-25.
7. Banks WA. Drug delivery to the brain in Alzheimer's disease: consideration of the blood-brain barrier. Adv Drug Deliv Rev 2012; 64: 629-639.
8. Engelhardt B, Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 2009; 31: 497-511.
9. Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 2010; 68: 409-427.
10. Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for bloodbrain barrier integrity during embryogenesis. Nature 2010; 468: 562-566.
11. Balabanov R, Dore-Duffy P. Role of the CNS microvascular pericyte in the bloodbrain barrier. J Neurosci Res 1998; 53: 637-644. (Pubitemid 28423871)
12. Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C et al. Pericytes regulate the blood-brain barrier. Nature 2010; 468: 557-561.
13. Abbott NJ. Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 2002; 200: 629-638. (Pubitemid 34823054)
14. Tibbling G, Link H, Thman S. Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. Scand J Clin Lab Invest 1977; 37: 385-390. (Pubitemid 8387871)
15. Alafuzoff I, Adolfsson R, Bucht G, Winblad B. Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia. J Neurol Sci 1983; 60: 465-472. (Pubitemid 13051197)
16. Elovaara I, Icén A, Palo J, Erkinjuntti T. CSF in Alzheimer's disease. Studies on blood-brain barrier function and intrathecal protein synthesis. J Neurol Sci 1985; 70: 73-80. (Pubitemid 15019901)
17. Hampel H, Kö tter HU, Mö ller HJ. Blood-cerebrospinal fluid barrier dysfunction for high molecular weight proteins in Alzheimer disease and major depression: indication for disease subsets. Alzheimer Dis Assoc Disord 1997; 11: 78-87. (Pubitemid 27271977)
18. Wada H. Blood-brain barrier permeability of the demented elderly as studied by cerebrospinal fluid-serum albumin ratio. Intern Med 1998; 37: 509-513. (Pubitemid 128520872)
19. Skoog I, Wallin A, Fredman P, Hesse C, Aevarsson O, Karlsson I et al. A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer's disease and vascular dementia. Neurology 1998; 50: 966-971. (Pubitemid 28212823)
20. Algotsson A, Winblad B. The integrety of the blood-brain barrier in Alzheimer's Disease. Acta Neurol Scand 2007; 115: 403-408. (Pubitemid 46776325)
21. Bowman GL, Kaye JA, Moore M, Waichunas D, Carlson NE, Quinn JF. Blood-brain barrier impairment in Alzheimer's diease: stability and functional significance. Neurology 2007; 68: 1809-1814. (Pubitemid 46791393)
22. Blennow K, Wallin A, Fredman P, Karlsson I, Gottfries CG, Svennerholm L. Bloodbrain barrier disturbance in patients with Alzheimer's disease is related to vascular factors. Acta Neurol Scand 1990; 81: 323-326. (Pubitemid 20174132)
23. Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease-systematic review and metaanalysis. Neurobiol Aging 2007; 30: 337-352.
24. Chalbot S, Zetterberg H, Blennow K, Fladby T, Andreasen N, Grundke-Iqbal I et al. Blood-cerebrospinal fluid barrier permeability in Alzheimer's disease. J Alzheimers Dis 2011; 25: 505-515.
25. Hampel H, Kö tter HU, Padberg F, Kö rschenhausen DA, Mö ller HJ. Oligoclonal bands and blood-cerebrospinal-fluid barrier dysfunction in a subset of patients with Alzheimer disease: comparison with vascular dementia, major depression, and multiple sclerosis. Alzheimer Dis Assoc Disord 1999; 13: 9-19. (Pubitemid 29176517)
26. Mecocci P, Parnetti L, Reboldi GP, Santucci C, Gaiti A, Ferri C et al. Blood-brainbarrier in a geriatric population: barrier function in degenerative and vascular dementias. Acta Neurol Scand 1991; 84: 210-213.
27. Kay AD, May C, Papadopoulos NM, Costello R, Atack JR, Luxenberg JS et al. CSF and serum concentrations of albumin and IgG in Alzheimer's disease. Neurobiol Aging 1987; 8: 21-25. (Pubitemid 17034561)
28. Frolich L, Kornhuber J, Ihl R, Fritze J, Maurer K, Riederer P. Integrity of the blood-CSF barrier in dementia of Alzheimer type: CSF/serum ratios of albumin and IgG. Eur Arch Psychiatry Clin Neurosci 1991; 240: 363-366.
29. Chen R. Is it appropriate to use albumin CSF/plasma ratio to assess blood brain barrier permeability? Neurobiol Aging 2011; 32: 1338-1339.
30. Iemolo F, Duro G, Rizzo C, Castiglia L, Hachinski V, Caruso C. Pathophysiology of vascular dementia. Immun Ageing 2009; 6: 13.
31. Silverberg GD, Heit G, Huhn S, Jaffe RA, Chang SD, Bronte-Stewart H et al. The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer's type. Neurology 2001; 57: 1763-1766. (Pubitemid 33096680)
32. Wisniewski HM, Kozlowski PB. Evidence for blood-brain barrier changes in senile dementia of the Alzheimer type (SDAT). Ann NY Acad Sci 1982; 396: 119-129. (Pubitemid 13073501)
33. Wisniewski HM, Vorbrodt AW, Wegeil J. Amyloid angiopathy and blood-brain barrier changes in Alzheimer's disease. Ann NY Acad Sci 1997; 826: 161-172. (Pubitemid 27478038)
34. Siemmon JR, Hughes CM, Campbell GA, Flood DG. Increased levels of hemoglobin-derived and other peptides in Alzheimer's disease cerebellum. J Neurosci 1994; 14: 2225-2235. (Pubitemid 24108129)
35. De Reuck JL. The significance of small cerebral bleeds in neurodegenerative dementia syndromes. Aging Dis 2012; 3: 307-312.
36. Zipser BD, Johanson CD, Gonzalez L, Berzin TM, Tavares R, Hulette CN et al. Microvascular injury and blood-brain barrier leakage in Alzheimer's disease. Neurobiol Aging 2007; 28: 977-986. (Pubitemid 46635913)
37. Weinstein JR, Gold SJ, Cunningham DD, Gall CM. Cellular localization of thrombin receptor mRNA in Rat brain: expression by mesencephalic dopaminergenic neurons and codistribution with prothrombin mRNA. J Neurosci 1995; 15: 2906-2919.
38. Yamahata H, Takeshima H, Kuratsu JI, Sarker KP, Tanioka K, Wakimaru N et al. The role of thrombin in the neo-bascularization of malignant gliomas: an intrinsic modulator for the up-regulation of vascular endothelial growth factor. Int J Oncol 2002; 20: 921-928.
39. Claudio L. Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients. Acta Neuropathol 1996; 91: 6-14.
40. Alafuzoff I, Adolfsson R, Grundke-Iqbal I, Winblad B. Blood-brain barrier in Alzheimer dementia and in non-demented elderly. Acta Neuropathol (Berlin) 1987; 73: 160-166. (Pubitemid 17060012)
41. Rozemuller JM, Eikelenboom P, Kamphorst W, Stam FC. Lack of evedence for dysfunction of the blood-brain barrier in Alzheimer's disease: an immunohistochemical study. Neurobiol Aging 1988; 9: 383-391. (Pubitemid 19262071)
42. Tomimoto H, Akiguchi I, Suenaga T, Nishimura M, Wakita H, Nakamura S et al. Alterations of the blood-brain barrier and glial cells in white-matter lesions in cerebrovascular and Alzheimer's disease patients. Stroke 1996; 27: 2069-2074. (Pubitemid 26372583)
43. Munoz DG, Erkinjuntti T, Gaytan-Garcia S, Hachinski V. Serum protein leakage in Alzheimer's disease revisited. Ann NY Acad Sci 1997; 826: 173-189. (Pubitemid 27478039)
44. Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage C-A et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012; 78: 1043-1040.
45. Caserta MT, Caccioppo D, Lapin GD, Ragin A, Groothuis DR. Blood-brain barrier integrity in Alzheimer's disease patients and elderly control subjects. J Neuropsychiatry Clin Neurosci 1998; 10: 78-84. (Pubitemid 28135127)
46. Dysken MW, Nelson MJ, Hoover KM, Kuskowski M, McGeachie R. Rapid dynamic CT scanning in primary degenerative dementia and age-matched controls. Biol Psychiatry 1990; 28: 425-434. (Pubitemid 20245640)
47. Schlageter NL, Carson RE, Rapoport SI. Examination of blood-brain barrier permeability in dementia of the Alzheimer type with [68Ga]EDTA and positron emission tomography. J Cereb Blood Flow Metab 1987; 7: 1-8. (Pubitemid 17018308)
48. Starr JM, Farrall AJ, Armitage P, McGurn B, Wardlaw J. Blood-brain barrier permeability in Alzheimer's disease: a case-control MRI study. Psychiatry Res 2009; 171: 232-241.
49. Bronge L, Wahlund LO. White matter lesions in dementia: an MRI study on blood-brain barrier dysfunction. Dement Geriatr Cogn Disord 2000; 11: 263-267. (Pubitemid 30665928)
50. Wang H, Golob EJ, Su MY. Vascular volume and blood-brain barrier permeability measured by dynamic contrast enhanced MRI in hippocampus and cerebellum of patients with MCI and normal controls. J Magn Reson Imaging 2006; 24: 695-700. (Pubitemid 44320575)
51. Ghersi-Egea JF, Gorevic PD, Ghiso J, Frangione B, Patlak CS, Fenstermacher JD. Fate of cerebrospinal fluid-borne amyloid beta-peptide: rapid clearance into blood and appreciable accumulation by cerebral arteries. J Neurochem 1996; 67: 880-883. (Pubitemid 26255689)
52. Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B et al. Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 2000; 106: 1489-1499. (Pubitemid 32038587)
53. Donahue JE, Flaherty SL, Johanson CE, Duncan 3rd JA, Silverberg GD, Miller MC et al. RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease. Acta Neuropathol 2006; 112: 405-415. (Pubitemid 44469161)
54. Jaeger LB, Dohgu S, Hwang MC, Farr SA, Murphy MP, Fleegal-DeMotta MA et al. Testing the neurovascular hypothesis of Alzheimer's disease: LRP-1 antisense reduces blood-brain barrier clearance, increases brain levels of amyloid-beta protein, and impairs cognition. J Alzheimers Dis 2009; 17: 553-570.
55. Kandimalla KK, Curran GL, Holasek SS, Gilles EJ, Wengenack TM, Poduslo JF. Pharmacokinetic analysis of the blood-brain barrier transport of 125I-amyloid beta protein 40 in wild-type and Alzheimer's disease transgenic mice (APP,PS1) and its implications for amyloid plaque formation. J Pharmacol Exp Ther 2005; 313: 1370-1378. (Pubitemid 40727044)
56. Banks WA, Robinson SM, Verma S, Morley JE. Efflux of human and mouse amyloid beta proteins 1-40 and 1-42 from brain: impairment in a mouse model of Alzheimer's disease. Neuroscience 2003; 121: 487-492. (Pubitemid 37176936)
57. Bading JR, Yamada S, Mackic JB, Kirkman L, Miller C, Calero M et al. Brain clearance of Alzheimer's amyloid-beta40 in the squirrel monkey: a SPECT study in a primate model of cerebral amyloid angiopathy. J Drug Target 2002; 10: 359-368. (Pubitemid 34746318)
58. Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC et al. Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science 2010; 330: 1774.
59. Lam FC, Liu R, Lu P, Shapiro AB, Renoir JM, Sharom FJ et al. beta-Amyloid efflux mediated by p-glycoprotein. J Neurochem 2001; 76: 1121-1128.
60. Kuhnke D, Jedlitschky G, Grube M, Krohn M, Jucker M, Mosyagin I et al. MDR1-P-Glycoprotein (ABCB1) mediates transport of Alzheimer's amyloid-beta peptides-implications for the mechanisms of Abeta clearance at the bloodbrain barrier. Brain Pathol 2007; 17: 347-353. (Pubitemid 47537591)
61. Vogelgesang S, Cascorbi I, Schroeder E, Pahnke J, Kroemer HK, Siegmund W et al. Deposition of Alzheimer's beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics 2002; 12: 535-541. (Pubitemid 35177083)
62. Cirrito JR, Deane R, Fagan AM, Spinner ML, Parsadanian M, Finn MB et al. P-glycoprotein deficiency at the blood-brain barrier increases amyloid-beta deposition in an Alzheimer disease mouse model. J Clin Invest 2005; 115: 3285-3290. (Pubitemid 41567593)
63. Hartz AM, Miller DS, Bauer B. Restoring blood-brain barrier P-glycoprotein reduces brain amyloid-beta in a mouse model of Alzheimer's disease. Mol Pharmacol 2010; 77: 715-723.
64. van Assema DM, Lubberink M, Bauer M, van der Flier WM, Schuit RC, Windhorst AD et al. Blood-brain barrier P-glycoprotein function in Alzheimer's disease. Brain 2012; 135: 181-189.
65. Beaulieu E, Demeule M, Ghitescu L, Beliveau R. P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain. Biochem J 1997; 326(Pt 2): 539-544. (Pubitemid 27417234)
66. Erickson MA, Hansen K, Banks WA. Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood-brain barrier: protection by the antioxidant N-acetylcysteine. Brain Behav Immun 2012; 26: 1085-1094.
67. Candela P, Gosselet F, Saint-Pol J, Sevin E, Boucau MC, Boulanger E et al. Apical-to-basolateral transport of amyloid-beta peptides through bloodbrain barrier cells is mediated by the receptor for advanced glycation end-products and is restricted by P-glycoprotein. J Alzheimers Dis 2010; 22: 849-859.
68. Pflanzner T, Petsch B, Andre-Dohmen B, Muller-Schiffmann A, Tschickardt S, Weggen S et al. Cellular prion protein participates in amyloid-beta transcytosis across the blood-brain barrier. J Cereb Blood Flow Metab 2012; 32: 628-632.
69. Do TM, Noel-Hudson MS, Ribes S, Besengez C, Smirnova M, Cisternino S et al. ABCG2-and ABCG4-mediated efflux of amyloid-beta peptide 1-40 at the mouse blood-brain barrier. J Alzheimers Dis 2012; 30: 155-166.
70. Hortschansky P, Schroeckh V, Christopeit T, Zandomeneghi G, Fandrich M. The aggregation kinetics of Alzheimer's beta-amyloid peptide is controlled by stochastic nucleation. Protein Sci 2005; 14: 1753-1759. (Pubitemid 40994145)
71. Deane R, Wu Z, Sagare A, Davis J, Du Yan S, Hamm K et al. LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 2004; 43: 333-344. (Pubitemid 39061126)
72. Ito S, Ohtsuki S, Kamiie J, Nezu Y, Terasaki T. Cerebral clearance of human amyloid-beta peptide (1-40) across the blood-brain barrier is reduced by selfaggregation and formation of low-density lipoprotein receptor-related protein-1 ligand complexes. J Neurochem 2007; 103: 2482-2490. (Pubitemid 350173573)
73. Brenn A, Grube M, Peters M, Fischer A, Jedlitschky G, Kroemer HK et al. Betaamyloid downregulates MDR1-P-glycoprotein (Abcb1) expression at the bloodbrain barrier in mice. Int J Alzheimers Dis 2011; 2011: 690121.
74. Kumar VB, Farr SA, Flood JF, Kamlesh V, Franko M, Banks WA et al. Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice. Peptides 2000; 21: 1769-1775. (Pubitemid 32058851)
75. Morley JE, Kumar VB, Bernardo AE, Farr SA, Uezu K, Tumosa N et al. Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory. Peptides 2000; 21: 1761-1767. (Pubitemid 32058850)
76. Banks WA, Kumar VB, Farr SA, Nakaoke R, Robinson SM, Morley JE. Impairments in brain-to-blood transport of amyloid-beta and reabsorption of cerebrospinal fluid in an animal model of Alzheimer's disease are reversed by antisense directed against amyloid-beta protein precursor. J Alzheimers Dis 2011; 23: 599-605.
77. Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D et al. Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. Nature 1992; 359: 325-327.
78. Banks WA, Kastin AJ, Barrera CM, Maness LM. Lack of saturable transport across the blood-brain barrier in either direction for beta-amyloid1-28 (Alzheimer's disease protein). Brain Res Bull 1991; 27: 819-823.
79. Zlokovic BV, Ghiso J, Mackic JB, McComb JG, Weiss MH, Frangione B. Blood-brain barrier transport of circulating Alzheimer's amyloid beta. Biochem Biophys Res Commun 1993; 197: 1034-1040. (Pubitemid 24042727)
80. Maness LM, Banks WA, Podlisny MB, Selkoe DJ, Kastin AJ. Passage of human amyloid beta-protein 1-40 across the murine blood-brain barrier. Life Sci 1994; 55: 1643-1650. (Pubitemid 24339437)
81. Martel CL, Mackic JB, McComb JG, Ghiso J, Zlokovic BV. Blood-brain barrier uptake of the 40 and 42 amino acid sequences of circulating Alzheimer's amyloid beta in guinea pigs. Neurosci Lett 1996; 206: 157-160. (Pubitemid 26096445)
82. Poduslo JF, Curran GL, Haggard JJ, Biere AL, Selkoe DJ. Permeability and residual plasma volume of human, Dutch variant, and rat amyloid beta-protein 1-40 at the blood-brain barrier. Neurobiol Dis 1997; 4: 27-34. (Pubitemid 27509275)
83. Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9: 907-913. (Pubitemid 36889934)
84. Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B et al. A multimodal RAGEspecific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 2012; 122: 1377-1392.
85. Miller MC, Tavares R, Johanson CE, Hovanesian V, Donahue JE, Gonzalez L et al. Hippocampal RAGE immunoreactivity in early and advanced Alzheimer's disease. Brain Res 2008; 1230: 273-280.
86. Jeynes B, Provias J. Evidence for altered LRP/RAGE expression in Alzheimer lesion pathogenesis. Curr Alzheimer Res 2008; 5: 432-437.
87. Ghiso J, Shayo M, Calero M, Ng D, Tomidokoro Y, Gandy S et al. Systemic catabolism of Alzheimer's Abeta40 and Abeta42. J Biol Chem 2004; 279: 45897-45908. (Pubitemid 39491582)
88. Marques MA, Kulstad JJ, Savard CE, Green PS, Lee SP, Craft S et al. Peripheral amyloid-beta levels regulate amyloid-beta clearance from the central nervous system. J Alzheimers Dis 2009; 16: 325-329.
89. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 1996; 2: 864-870. (Pubitemid 26296755)
90. Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM. Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease. Arch Neurol 2000; 57: 100-105. (Pubitemid 30027637)
91. Graff-Radford NR, Crook JE, Lucas J, Boeve BF, Knopman DS, Ivnik RJ et al. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol 2007; 64: 354-362. (Pubitemid 46425689)
92. Pesaresi M, Lovati C, Bertora P, Mailland E, Galimberti D, Scarpini E et al. Plasma levels of beta-amyloid (1-42) in Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 2006; 27: 904-905. (Pubitemid 44287903)
93. Tamaoka A, Fukushima T, Sawamura N, Ishikawa K, Oguni E, Komatsuzaki Y et al. Amyloid beta protein in plasma from patients with sporadic Alzheimer's disease. J Neurol Sci 1996; 141: 65-68. (Pubitemid 26297732)
94. Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E et al. Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment. Neurobiol Aging 2010; 31: 357-367.
95. Biere AL, Ostaszewski B, Stimson ER, Hyman BT, Maggio JE, Selkoe DJ. Amyloid beta-peptide is transported on lipoproteins and albumin in human plasma. J Biol Chem 1996; 271: 32916-32922. (Pubitemid 27008725)
96. Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M et al. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA 1993; 90: 8098-8102. (Pubitemid 23260862)
97. Ghiso J, Matsubara E, Koudinov A, Choi-Miura NH, Tomita M, Wisniewski T et al. The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex. Biochem J 1993; 293(Pt 1): 27-30. (Pubitemid 23223142)
98. Sagare A, Deane R, Bell RD, Johnson B, Hamm K, Pendu R et al. Clearance of amyloid-beta by circulating lipoprotein receptors. Nat Med 2007; 13: 1029-1031. (Pubitemid 47517512)
99. Deane R, Sagare A, Zlokovic BV. The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. Curr Pharm Des 2008; 14: 1601-1605. (Pubitemid 352002987)
100. Pan W, Solomon B, Maness LM, Kastin AJ. Antibodies to beta-amyloid decrease the blood-to-brain transfer of beta-amyloid peptide. Exp Biol Med (Maywood) 2002; 227: 609-615.
101. Matsuoka Y, Saito M, LaFrancois J, Gaynor K, Olm V, Wang L et al. Novel therapeutic approach for the treatment of Alzheimer's disease by peripheral administration of agents with an affinity to beta-amyloid. J Neurosci 2003; 23: 29-33. (Pubitemid 36050401)
102. Landau SM, Harvey D, Madison CM, Koeppe RA, Reiman EM, Foster NL et al. Associations between cognitive, functional, and FDG-PET measrues of decline in AD and MCI. Neurobiol Aging 2011; 32: 1207-1278.
103. Oldendorf WH. Brain uptake of radio-labelled amino acids, amines and hexoses after arterial injection. Am J Physiol 1971; 221: 1629-1639.
104. De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 1991; 325: 703-709.
105. Harik SI. Changes in the glucose transporter of brain capillaries. Can J Physiol Pharmacol 1992; 70 S1: S113-S117. (Pubitemid 23091614)
106. Horwood N, Davies DC. Immunolabelling of hippocampal microvessel glucose transporter protein is reduced in Alzheimer's disease. Virchows Arch 1994; 425: 69-72. (Pubitemid 24295508)
107. Kalaria RN, Harik SI. Abnormalities of the glucose transporter at the blood-brain barrier and in brain in Alzheimer's disease. Prog Clin Biol Res 1989; 317: 415-421.
108. Mooradian AD, Chung HC, Shah GN. GLUT-1 expression in the cerebra of patients with Alzheimer's disease. Neurobiol Aging 1997; 18: 469-474. (Pubitemid 27497142)
109. Harik SI, Kalaria RN. Blood-brain barrier abnormalities in Alzheimer's disease. Ann NY Acad Sci 1991; 640: 47-52.
110. Hooijmans CR, Graven C, Dederen PJ, Tanila H, van Groen T, Kiliaan AJ. Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain Res 2007; 1181: 93-103. (Pubitemid 350050914)
111. Lehmann M, Ghosh PM, Madison C, Laforce RJ, Corbetta-Rastelli C, WEiner MW et al. Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer's disease. Brain 2013; 136(Pt): 844-858.
112. Jagust WJ, Landau SM. Initiative AsDN. Apolipoprotein E, not fibrillar betaamyloid, reduces cerebral glucose metabolism in normal aging. J Neurosci 2012; 32: 18227-18233.
113. Johanson CE, Stopa EG, McMillan PN. The blood-cerebrospinal fluid barrier: structure and functional significance. Methods Mol Biol 2011; 686: 101-131.
114. Silverberg GD, Mayo M, Saul T, Rubenstein E, McGuire D. Alzheimer's disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesis. Lancet Neurol 2003; 2: 506-511. (Pubitemid 36876108)
115. Henriksson L, Voigt K. Age-dependent differences of distribution and clearance patterns in normal RIHSA cisternograms. Neuroradiology 1976; 12: 103-107.
116. Preston JE. Ageing choroid plexus-cerebrospinal fluid system. Microsc Res Tech 2001; 52: 31-37. (Pubitemid 32065026)
117. Oldendorf WH, Davson H. Brain extracellular space and the sink action of cerebrospinal fluid. Measurement of rabbit brain extracellular space using sucrose labeled with carbon 14. Arch Neurol 1967; 17: 196-205.
118. Abbott NJ. Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int 2004; 45: 545-552. (Pubitemid 38739482)
119. Rennels ML, Gregory TF, Blaumanis OR, Fujimoto K, Grady PA. Evidence for a 'paravascular' fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res 1985; 326: 47-63. (Pubitemid 15160009)
120. Rennels ML, Blaumanis OR, Grady PA. Rapid solute transport throughout the brain via paravascular fluid pathways. Adv Neurol 1990; 52: 431-439.
121. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 2012; 4: 147ra111.
122. Bell RD, Deane R, Chow N, Long X, Sagare A, Singh I et al. SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat Cell Biol 2009; 11: 143-153.
123. Kanekiyo T, Liu CC, Shinohara M, Li J, Bu G. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-beta. J Neurosci 2012; 32: 16458-16465.
124. Weller RO, Massey A, Kuo YM, Roher AE. Cerebral amyloid angiopathy: accumulation of A beta in interstitial fluid drainage pathways in Alzheimer's disease. Ann NY Acad Sci 2000; 903: 110-117. (Pubitemid 30251546)
125. Jellinger KA. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 2002; 109: 813-836. (Pubitemid 34810776)
126. Moftakhar P, Lynch MD, Pomakian JL, Vinters HV. Aquaporin expression in the brains of patients with or without cerebral amyloid angiopathy. J Neuropathol Exp Neurol 2010; 69: 1201-1209.
127. Wilcock DM, Vitek MP, Colton CA. Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. Neuroscience 2009; 159: 1055-1069.
128. Yang W, Wu Q, Yuan C, Gao J, Xiao M, Gu M et al. Aquaporin-4 mediates astrocyte response to beta-amyloid. Mol Cell Neurosci 2012; 49: 406-414.
129. Rauch SM, Huen K, Miller MC, Chaudry H, Lau M, Sanes JR et al. Changes in brain beta-amyloid deposition and aquaporin 4 levels in response to altered agrin expression in mice. J Neuropathol Exp Neurol 2011; 70: 1124-1137.
130. Oshio K, Watanabe H, Song Y, Verkman AS, Manley GT. Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1. FASEB J 2005; 19: 76-78. (Pubitemid 40069923)
131. McCoy E, Sontheimer H. MAPK induces AQP1 expression in astrocytes following injury. Glia 2010; 58: 209-217.
132. Hoshi A, Yamamoto T, Shimizu K, Ugawa Y, Nishizawa M, Takahashi H et al. Characteristics of aquaporin expression surrounding senile plaques and cerebral amyloid angiopathy in Alzheimer disease. J Neuropathol Exp Neurol 2012; 71: 750-759.
133. Perez E, Barrachina M, Rodriguez A, Torrejon-Escribano B, Boada M, Hernandez I et al. Aquaporin expression in the cerebral cortex is increased at early stages of Alzheimer disease. Brain Res 2007; 1128: 164-174. (Pubitemid 46048625)
134. Misawa T, Arima K, Mizusawa H, Satoh J. Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains. Acta Neuropathol 2008; 116: 247-260.
135. Crossgrove JS, Li GJ, Zheng W. The choroid plexus removes beta-amyloid from brain cerebrospinal fluid. Exp Biol Med (Maywood) 2005; 230: 771-776. (Pubitemid 41565947)
136. Fujiyoshi M, Tachikawa M, Ohtsuki S, Ito S, Uchida Y, Akanuma S et al. Amyloidbeta peptide(1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier. J Neurochem 2011; 118: 407-415.
137. Zlokovic BV, Martel CL, Matsubara E, McComb JG, Zheng G, McCluskey RT et al. Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers. Proc Natl Acad Sci USA 1996; 93: 4229-4234.
138. Rao VV, Dahlheimer JL, Bardgett ME, Snyder AZ, Finch RA, Sartorelli AC et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drugpermeability barrier. Proc Natl Acad Sci USA 1999; 96: 3900-3905. (Pubitemid 29169008)
139. Pascale CL, Miller MC, Chiu C, Boylan M, Caralopoulos IN, Gonzalez L et al. Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent. Fluids Barriers CNS 2011; 8: 21.
140. Vargas T, Ugalde C, Spuch C, Antequera D, Moran MJ, Martin MA et al. Abeta accumulation in choroid plexus is associated with mitochondrial-induced apoptosis. Neurobiol Aging 2010; 31: 1569-1581.
141. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57: 173-185. (Pubitemid 41043883)
142. Sa-Pereira I, Brites D, Brito MA. Neurovascular unit: a focus on pericytes. Mol Neurobiol 2012; 45: 327-347.
143. Nakagawa S, Deli MA, Nakao S, Honda M, Hayashi K, Nakaoke R et al. Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol 2007; 27: 687-694. (Pubitemid 47476613)
144. Dore-Duffy P, Katychev A, Wang X, Van Buren E. CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab 2006; 26: 613-624.
145. Sengillo JD, Winkler EA, Walker CT, Sullivan JS, Johnson M, Zlokovic BV. Deficiency in mural vascular cells coincides with blood-brain barrier disruption in Alzheimer's disease. Brain Pathol 2013; 23: 303-310.
146. Verbeek MM, de Waal RM, Schipper JJ, Van Nostrand WE. Rapid degeneration of cultured human brain pericytes by amyloid beta protein. J Neurochem 1997; 68: 1135-1141. (Pubitemid 27086218)
147. Fernandez-Klett F, Potas JR, Hilpert D, Blazej K, Radke J, Huck J et al. Early loss of pericytes and perivascular stromal cell-induced scar formation after stroke. J Cereb Blood Flow Metab 2012; 33: 428-439.
148. Dore-Duffy P, Owen C, Balabanov R, Murphy S, Beaumont T, Rafols JA. Pericyte migration from the vascular wall in response to traumatic brain injury.
149. Price TO, Eranki V, Banks WA, Ercal N, Shah GN. Topiramate treatment protects blood-brain barrier pericytes from hyperglycemia-induced oxidative damage in diabetic mice. Endocrinology 2012; 153: 362-372.
150. Peppiatt CM, Howarth C, Mobbs P, Attwell D. Bidirectional control of CNS capillary diameter by pericytes. Nature 2006; 443: 700-704. (Pubitemid 44564713)
151. Prior R, Wihl G, Urmoneit B. Apolipoprotein E, smooth muscle cells and the pathogenesis of cerebral amyloid angiopathy: the potential role of impaired cerebrovascular A beta clearance. Ann NY Acad Sci 2000; 903: 180-186. (Pubitemid 30251557)
152. Tooyama I, Kawamata T, Akiyama H, Kimura H, Moestrup SK, Gliemann J et al. Subcellular localization of the low density lipoprotein receptor-related protein (alpha 2-macroglobulin receptor) in human brain. Brain Res 1995; 691: 235-238.
153. Kovac A, Erickson MA, Banks WA. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide. J Neuroinflammation 2011; 8: 139.
154. Thal DR. The role of astrocytes in amyloid beta-protein toxicity and clearance. Exp Neurol 2012; 236: 1-5.
155. Thal DR. The pre-capillary segment of the blood-brain barrier and its relation to perivascular drainage in Alzheimer's disease and small vessel disease. ScientificWorldJournal 2009; 9: 557-563.
156. Wolburg H, Neuhaus J, Kniesel U, Krauss B, Schmid EM, Ocalan M et al. Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. J Cell Sci 1994; 107(Pt 5): 1347-1357. (Pubitemid 24177334)
157. Arthur FE, Shivers RR, Bowman PD. Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model. Brain Res 1987; 433: 155-159. (Pubitemid 18005987)
158. El Hafny B, Chappey O, Piciotti M, Debray M, Boval B, Roux F. Modulation of P-glycoprotein activity by glial factors and retinoic acid in an immortalized rat brain microvessel endothelial cell line. Neurosci Lett 1997; 236: 107-111. (Pubitemid 27496232)
159. Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F et al. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 2003; 9: 453-457. (Pubitemid 36460080)
160. Pihlaja R, Koistinaho J, Kauppinen R, Sandholm J, Tanila H, Koistinaho M. Multiple cellular and molecular mechanisms are involved in human Abeta clearance by transplanted adult astrocytes. Glia 2011; 59: 1643-1657.
161. Pike CJ, Cummings BJ, Cotman CW. Early association of reactive astrocytes with senile plaques in Alzheimer's disease. Exp Neurol 1995; 132: 172-179.
162. Mulder SD, Veerhuis R, Blankenstein MA, Nielsen HM. The effect of amyloid associated proteins on the expression of genes involved in amyloid-beta clearance by adult human astrocytes. Exp Neurol 2012; 233: 373-379.
163. Matos M, Augusto E, Oliveira CR, Agostinho P. Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: involvement of oxidative stress and mitogen-activated protein kinase cascades. Neuroscience 2008; 156: 898-910.
164. Rodriguez JJ, Olabarria M, Chvatal A, Verkhratsky A. Astroglia in dementia and Alzheimer's disease. Cell Death Differ 2009; 16: 378-385.
165. Merlini M, Meyer EP, Ulmann-Schuler A, Nitsch RM. Vascular beta-amyloid and early astrocyte alterations impair cerebrovascular function and cerebral metabolism in transgenic arcAbeta mice. Acta Neuropathol 2011; 122: 293-311.
166. Guillemin GJ, Brew BJ. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. Jo Leukoc Biol 2004; 75: 388-397. (Pubitemid 38316367)
167. Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005; 308: 1314-1318. (Pubitemid 40746128)
168. Rogers J, Lue LF. Microglial chemotaxis, activation, and phagocytosis of amyloid beta-peptide as linked phenomena in Alzheimer's disease. Neurochem Int 2001; 39: 333-340. (Pubitemid 32907397)
169. Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE et al. Microglia, amyloid, and cognition in Alzheimer's disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis 2008; 32: 412-419.
170. Wisniewski HM, Barcikowska M, Kida E. Phagocytosis of beta/A4 amyloid fibrils of the neuritic neocortical plaques. Acta Neuropathol 1991; 81: 588-590.
171. Simard AR, Soulet D, Gowing G, Julien JP, Rivest S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 2006; 49: 489-502. (Pubitemid 43221886)
172. Hawkes CA, McLaurin J. Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc Natl Acad Sci USA 2009; 106: 1261-1266.
173. Avagyan H, Goldenson B, Tse E, Masoumi A, Porter V, Wiedau-Pazos M et al. Immune blood biomarkers of Alzheimer disease patients. J Neuroimmunol 2009; 210: 67-72.
174. Nicolakakis N, Hamel E. Neurovascular function in Alzheimer's disease patients and experimental models. J Cereb Blood Flow Metab 2011; 31: 1354-1370.
175. Grammas P, Sanchez A, Tripathy D, Luo E, Martinez J. Vascular signaling abnormalities in Alzheimer disease. Cleve Clin J Med 2011; 78(Suppl 1): S50-S53.
176. Yin X, Wright J, Wall T, Grammas P. Brain endothelial cells synthesize neurotoxic thrombin in Alzheimer's disease. Am J Pathol 2010; 176: 1600-1606.
177. Luo J, Grammas P. Endothelin-1 is elevated in Alzheimer's disease brain microvessels and is neuroprotective. J Alzheimers Dis 2010; 21: 887-896.
178. Tripathy D, Thirumangalakudi L, Grammas P. RANTES upregulation in the Alzheimer's disease brain: a possible neuroprotective role. Neurobiol Aging 2010; 31: 8-16.
179. Grammas P, Moore P, Weigel PH. Microvessels from Alzheimer's disease brains kill neurons in vitro. Am J Pathol 1999; 154: 337-342. (Pubitemid 29094084)
180. Sanchez A, Tripathy D, Luo J, Yin X, Martinez J, Grammas P. Neurovascular unit and the effects of dosage in VEGF toxicity: role for oxidative stress and thrombin. J Alzheimers Dis 2013; 34: 281-291.
181. Fagan SC, Hess DC, Hohnadel EJ, Pollock DM, Ergul A. Targets for vascular protection after acute ischemic stroke. Stroke 2004; 35: 2220-2225. (Pubitemid 39129589)
182. Wick A, Wick W, Waltenberger J, Weller M, Dichgans J, Schulz JB. Neuroprotection by hypoxic preconditioning requires sequential activation of vascular endothelial growth factor receptor and Akt. J Neurosci 2002; 22: 6401-6407. (Pubitemid 35386396)
183. Tolosa L, Mir M, Asensio VJ, Olmos G, Llado J. Vascular endothelial growth factor protects spinal cord motoneurons against glutamate-induced excitotoxicity via phosphatidylinositol 3-kinase. J Neurochem 2008; 105: 1080-1090. (Pubitemid 351590778)
184. Perry G, Cash AD, Smith MA. Alzheimer disease and oxidative stress. J Biomed Biotechnol 2002; 2: 120-123. (Pubitemid 44204507)
185. Eikelenboom P, van Exel E, Veerhuis R, Rozemuller AJ, van Gool WA, Hoozemans JJ. Innate immunity and the etiology of late-onset Alzheimer's disease. Neurodegener Dis 2012; 10: 271-273.
186. Pan W, Stone KP, Hsuchou H, Manda VK, Zhang Y, Kastin AJ. Cytokine signaling modulates blood-brain barrier function. Curr Pharm Des 2011; 17: 3729-3740.
187. Bannerman DD, Goldblum SE. Direct effects of endotoxin on the endothelium: barrier function and injury. Lab Invest 1999; 79: 1181-1199. (Pubitemid 29489444)
188. Verma S, Nakaoke R, Dohgu S, Banks WA. Release of cytokines by brain endothelial cells: A polarized response to lipopolysaccharide. Brain Behav Immun 2006; 20: 449-455. (Pubitemid 44175796)
189. Gonzalez-Velasquez FJ, Kotarek JA, Moss MA. Soluble aggregates of the amyloidbeta protein selectively stimulate permeability in human brain microvascular endothelial monolayers. J Neurochem 2008; 107: 466-477.
190. Deli MA, Veszelka S, Csiszar B, Toth A, Kittel A, Csete M et al. Protection of the blood-brain barrier by pentosan against amyloid-beta-induced toxicity. J Alzheimers Dis 2010; 22: 777-794.
191. Carrano A, Hoozemans JJ, van der Vies SM, Rozemuller AJ, van Horssen J, de Vries HE. Amyloid Beta induces oxidative stress-mediated blood-brain barrier changes in capillary amyloid angiopathy. Antioxid Redox Signal 2011; 15: 1167-1178.
192. Kovac A, Zilkova M, Deli MA, Zilka N, Novak M. Human truncated tau is using a different mechanism from amyloid-beta to damage the blood-brain barrier. J Alzheimers Dis 2009; 18: 897-906.
193. Tada M, Diserens AC, Desbaillets I, de Tribolet N. Analysis of cytokine receptor messenger RNA expression in human glioblastoma cells and normal astrocytes by reverse-transcription polymerase chain reaction. J Neurosurg 1994; 80: 1063-1073. (Pubitemid 24154184)
194. Takata F, Dohgu S, Matsumoto J, Takahashi H, Machida T, Wakigawa T et al. Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-alpha, releasing matrix metalloproteinase-9 and migrating in vitro. J Neuroinflammation 2011; 8: 106.
195. Erickson MA, Hartvigson PE, Morofuji Y, Owen JB, Butterfield DA, Banks WA. Lipopolysaccharide impairs amyloid beta efflux from brain: altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier. J Neuroinflammation 2012; 9: 150.
196. Owen JB, Sultana R, Aluise CD, Erickson MA, Price TO, Bu G et al. Oxidative modification to LDL receptor-related protein 1 in hippocampus from subjects with Alzheimer disease: implications for Abeta accumulation in AD brain. Free Radic Biol Med 2010; 49: 1798-1803.
197. Nishida Y, Ito S, Ohtsuki S, Yamamoto N, Takahashi T, Iwata N et al. Depletion of vitamin E increases amyloid beta accumulation by decreasing its clearances from brain and blood in a mouse model of Alzheimer disease. J Biol Chem 2009; 284: 33400-33408.
198. Jaeger LB, Dohgu S, Sultana R, Lynch JL, Owen JB, Erickson MA et al. Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein: a mechanism for inflammation in the progression of Alzheimer's disease. Brain Behav Immun 2009; 23: 507-517.
199. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 1997; 278: 1349-1356. (Pubitemid 27449696)
200. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921-923. (Pubitemid 23275809)
201. Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 2013; 9: 106-118.
202. Martel CL, Mackic JB, Matsubara E, Governale S, Miguel C, Miao W et al. Isoformspecific effects of apolipoproteins E2, E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer's amyloid beta. J Neurochem 1997; 69: 1995-2004. (Pubitemid 27452746)
203. Bachmeier C, Paris D, Beaulieu-Abdelahad D, Mouzon B, Mullan M, Crawford F. A multifaceted role for apoE in the clearance of beta-amyloid across the blood-brain barrier. Neurodegener Dis 2013; 11: 13-21.
204. Deane R, Sagare A, Hamm K, Parisi M, Lane S, Finn MB et al. apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain. J Clin Invest 2008; 118: 4002-4013.
205. Ji Y, Permanne B, Sigurdsson EM, Holtzman DM, Wisniewski T. Amyloid beta40/42 clearance across the blood-brain barrier following intra-ventricular injections in wild-type, apoE knock-out and human apoE3 or E4 expressing transgenic mice. J Alzheimers Dis 2001; 3: 23-30. (Pubitemid 32238247)
206. Nishitsuji K, Hosono T, Nakamura T, Bu G, Michikawa 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: 17536-17542.
207. Bell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 2012; 485: 512-516.
208. Yang Y, Estrada EY, Thompson JF, Liu W, Rosenberg GA. Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 2007; 27: 697-709. (Pubitemid 46474608)
209. Yaffe K, Falvey C, Hamilton N, Schwartz AV, Simonsick EM, Satterfield S et al. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch Neurol 2012; 69: 1170-1175.
210. Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 2010; 67: 505-512.
211. Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A et al. Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 2012; 122: 1316-1338.
212. Banks WA, Owen JB, Erickson MA. Insulin in the brain: there and back again. Pharmacol Ther 2012; 136: 82-93.
213. de la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol 2008; 2: 1101-1113.
214. Lacroix MC, Badonnel K, Meunier N, Tan F, Schlegel-Le Poupon C, Durieux D et al. Expression of insulin system in the olfactory epithelium: first approaches to its role and regulation. J Neuroendocrinol 2008; 20: 1176-1190.
215. Woods SC, Seeley RJ, Baskin DG, Schwartz MW. Insulin and the blood-brain barrier. Curr Pharm Des 2003; 9: 795-800. (Pubitemid 36367601)
216. Schwartz MW, Bergman RN, Kahn SE, Taborsky Jr. GJ, Fisher LD, Sipols AJ et al. Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport. J Clin Invest 1991; 88: 1272-1281.
217. Baura GD, Foster DM, Porte Jr. D, Kahn SE, Bergman RN, Cobelli C et al. Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. A mechanism for regulated insulin delivery to the brain. J Clin Invest 1993; 92: 1824-1830. (Pubitemid 23304549)
218. Banks WA, Jaspan JB, Huang W, Kastin AJ. Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. Peptides 1997; 18: 1423-1429. (Pubitemid 27519755)
219. Banks WA, Jaspan JB, Kastin AJ. Effect of diabetes mellitus on the permeability of the blood-brain barrier to insulin. Peptides 1997; 18: 1577-1584. (Pubitemid 28133001)
220. Xaio H, Banks WA, Niehoff ML, Morley JE. Effect of LPS on the permeability of the blood-brain barrier to insulin. Brain Res 2001; 896: 36-42. (Pubitemid 32244144)
221. Urayama A, Banks WA. Starvation and triglycerides reverse the obesity-induced impairment of insulin transport at the blood-brain barrier. Endocrinology 2008; 149: 3592-3597. (Pubitemid 351919597)
222. Kaiyala KJ, Prigeon RL, Kahn SE, Woods SC, Schwartz MW. Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs. Diabetes 2000; 49: 1525-1533.
223. Baskin DG, Stein LJ, Ikeda H, Woods SC, Figlewicz DP, Porte Jr. D et al. Genetically obese Zucker rats have abnormally low brain insulin content. Life Sci 1985; 36: 627-633. (Pubitemid 15159768)
224. Hong H, Liu LP, Liao JM, Wang TS, Ye FY, Wu J et al. Downregulation of LRP1 [correction of LPR1] at the blood-brain barrier in streptozotocin-induced diabetic mice. Neuropharmacology 2009; 56: 1054-1059.
225. Liu LP, Hong H, Liao JM, Wang TS, Wu J, Chen SS et al. Upregulation of RAGE at the blood-brain barrier in streptozotocin-induced diabetic mice. Synapse 2009; 63: 636-642.
226. Reichel V, Burghard S, John I, Huber O. P-glycoprotein and breast cancer resistance protein expression and function at the blood-brain barrier and blood-cerebrospinal fluid barrier (choroid plexus) in streptozotocin-induced diabetes in rats. Brain Res 2011; 1370: 238-245.
227. Huber JD, VanGilder RL, Houser KA. Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats. Am J Physiol Heart Circ Physiol 2006; 291: H2660-H2668. (Pubitemid 44904065)
228. Starr JM, Wardlaw J, Ferguson K, MacLullich A, Deary IJ, Marshall I. Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J Neurol Neurosurg Psychiatry 2003; 74: 70-76. (Pubitemid 36069039)
229. Mandarino LJ. Current hypotheses for the biochemical basis of diabetic retinopathy. Diabetes Care 1992; 15: 1892-1901.
230. Alzheimer's Association. 2012 Alzheimer's disease facts and figures. Alzheimers Dement 2012; 8: 131-168.
231. Johnson VE, Stewart W, Smith DH. Traumatic brain injury and amyloid-beta pathology: a link to Alzheimer's disease? Nat Rev Neurosci 2010; 11: 361-370.
232. Pop V, Badaut JA. Neurovascular perspective for long-term changes after brain trauma. Transl Stroke Res 2011; 2: 533-545.
233. Pop V, Sorensen DW, Kamper JE, Ajao DO, Paul Murphy M, Head E et al. Early brain injury alters the blood-brain barrier phenotype in parallel with betaamyloid and cognitive changes in adulthood. J Cereb Blood Flow Metab 2013; 33: 205-214.
234. Brunswick AS, Hwang BY, Appelboom G, Hwang RY, Piazza MA, Connolly Jr. ES. Serum biomarkers of spontaneous intracerebral hemorrhage induced secondary brain injury. J Neurol Sci 2012; 321: 1-10.
235. Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012; 78: 1043-1050.
236. Honjo K, Black SE, Verhoeff NP. Alzheimer's disease, cerebrovascular disease, and the beta-amyloid cascade. Can J Neurol Sci 2012; 39: 712-728.
237. Han F, Fukunaga K. Beta-amyloid accumulation in neurovascular units following brain embolism. J Pharmacol Sci 2009; 111: 101-109.
238. Kalaria RN, Akinyemi R, Ihara M. Does vascular pathology contribute to Alzheimer changes? J Neurol Sci 2012; 322: 141-147.