Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease

Journal of Cerebral Blood Flow and Metabolism

Volumn 36, Issue 1, 2016, Pages 216-227

  Halliday, Matthew R ^a,b   Rege, Sanket V ^b   Ma, Qingyi ^b   Zhao, Zhen ^b   Miller, Carol A ^b   Winkler, Ethan A ^c   Zlokovic, Berisla V ^b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Alzheimer's; blood brain barrier; neurodegeneration; neurovascular unit; pericytes

Indexed keywords

APOLIPOPROTEIN E3; APOLIPOPROTEIN E4; CYCLOPHILIN A; FIBRIN; GELATINASE B; IMMUNOGLOBULIN G; LECTIN; LIPOPROTEIN RECEPTOR; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; ISOPROTEIN;

AGED; ALLELE; ALZHEIMER DISEASE; ARTICLE; BLOOD BRAIN BARRIER; CAPILLARY WALL; CELL DEGENERATION; CELL LOSS; CLINICAL ARTICLE; COHORT ANALYSIS; COMPARATIVE STUDY; CONTROLLED STUDY; ENDOTHELIUM CELL; FEMALE; GENOTYPE; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MALE; NONHUMAN; PERICYTE; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; VERY ELDERLY; CELL COUNT; GENETICS; METABOLISM; PATHOLOGY; VASCULAR ENDOTHELIUM;

AGED; AGED, 80 AND OVER; ALLELES; ALZHEIMER DISEASE; APOLIPOPROTEIN E4; BLOOD-BRAIN BARRIER; CELL COUNT; COHORT STUDIES; ENDOTHELIUM, VASCULAR; FEMALE; HUMANS; MALE; PERICYTES; PROTEIN ISOFORMS;

EID: 84951568640     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2015.44     Document Type: Article

References (40)

1. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008; 57: 178-201
2. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci 2011; 12: 723-738
3. Zlokovic B. Cerebrovascular permeability to peptides: manipulations of transport systems at the blood-brain barrier. Pharm Res 1995; 12: 1395-1406
4. Zlokovic BV, Lipovac MN, Begley DJ, Davson H and Rakic L. Transport of leucine-enkephalin across the blood-brain barrier in the perfused guinea pig brain. J Neurochem 1987; 49: 310-315
5. Zlokovic BV, Begley DJ and Chain-Eliash DG. Bloodbrain barrier permeability to leucine-enkephalin,d-Alanine2-d-leucine5-enkephalin and their N-terminal amino acid (tyrosine). Brain Res 1985; 336: 125-132
6. Armulik A, GenovéG, Mäe M, Nisancioglu MH, Wallgard E, Niaudet C, et al. Pericytes regulate the blood-brain barrier. Nature 2010; 468: 557-561
7. Daneman R, Zhou L, Kebede AA and Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010; 468: 562-566
8. 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
9. Winkler EA, Bell RD and Zlokovic BV. Central nervous system pericytes in health and disease. Nat Neurosci 2011; 14: 1398-1405
10. Farkas E and Luiten PG. Cerebral microvascular pathology in aging and Alzheimer's disease. Prog Neurobiol 2001; 64: 575-611
11. Baloyannis SJ and Baloyannis IS. The vascular factor in Alzheimer's disease: a study in Golgi technique and electron microscopy. J Neurol Sci 2012; 322: 117-121
12. Sengillo JD, Winkler EA, Walker CT, Sullivan JS, Johnson M and Zlokovic BV. Deficiency in mural vascular cells coincides with blood-brain barrier disruption in Alzheimer's disease. Brain Pathol 2013; 23: 303-310
13. Blennow K, Wallin A, Fredman P, Karlsson I, Gottfries CG and Svennerholm L. Blood-brain barrier disturbance in patients with Alzheimer's disease is related to vascular factors. Acta Neurol Scand 1990; 81: 323-326
14. Fiala M, Liu QN, Sayre J, Pop V, Brahmandam V, Graves MC, et al. Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier. Eur J Clin Invest 2002; 32: 360-371
15. Salloway S, Gur T, Berzin T, Tavares R, Zipser B, Correia S, et al. Effect of APOE genotype on microvascular basement membrane in Alzheimer's disease. J Neurol Sci 2002; 203-204: 1837
16. Cullen KM, Kócsi Z and Stone J. Pericapillary haem-rich deposits: evidence for microhaemorrhages in aging human cerebral cortex. J Cereb Blood Flow Metab 2005; 25: 1656-1667
17. Zipser BD, Johanson CE, Gonzalez L, Berzin TM, Tavares R, Hulette CM, et al. Microvascular injury and blood-brain barrier leakage in Alzheimer's disease. Neurobiol Aging 2007; 28: 977-986
18. Goos JD, Kester MI, Barkhof F, Klein M, Blankenstein MA, Scheltens P, et al. Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition fluid biomarkers and cognition. Stroke 2009; 40: 3455-3460
19. Ryu JK and McLarnon JG. A leaky blood-brain barrier, fibrinogen infiltration and microglial reactivity in inflamed Alzheimer's disease brain. J Cell Mol Med 2009; 13: 2911-2925
20. Farrall AJ and Wardlaw JM. Blood-brain barrier: ageing and microvascular disease-systematic review and metaanalysis. Neurobiol Aging 2009; 30: 337-352
21. Bowman GL, Kaye JA and Quinn JF. Dyslipidemia and blood-brain barrier integrity in Alzheimer's disease. Curr Gerontol Geriatr Res 2012; 2012: 184042
22. Hultman K, Strickland S and Norris EH. The APOE e4/e4 genotype potentiates vascular fibrin(ogen) deposition in amyloid-laden vessels in the brains of Alzheimer's disease patients. J Cereb Blood Flow Metab 2013; 33: 1251-1258
23. Halliday MR, Pomara N, Sagare AP, Mack WJ, Frangione B and Zlokovic BV. Relationship between cyclophilin a levels and matrix metalloproteinase 9 activity in cerebrospinal fluid of cognitively normal apolipoprotein e4 carriers and blood-brain barrier breakdown. JAMA Neurol 2013; 70: 1198-1200
24. Zonneveld HI, Goos JD, Wattjes MP, Prins ND, Scheltens P, van der Flier WM, et al. Prevalence of cortical superficial siderosis in a memory clinic population. Neurology 2014; 82: 698-704
25. Winkler EA, Sagare AP and Zlokovic BV. The pericyte: a forgotten cell type with important implications for Alzheimer's disease? Brain Pathol 2014; 24: 371-386
26. Kim J, Basak JM and Holtzman DM. The role of apolipoprotein E in Alzheimer's disease. Neuron 2009; 63: 287-303
27. Verghese PB, Castellano JM and Holtzman DM. Apolipoprotein E in Alzheimer's disease and other neurological disorders. Lancet Neurol 2011; 10: 241-252
28. Nishitsuji K, Hosono T, Nakamura T, Bu G and 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
29. 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
30. Alata W, Ye Y, St-Amour I, Vandal M and Calon F. Human apolipoprotein E e4 expression impairs cerebral vascularization and blood-brain barrier function in mice. J Cereb Blood Flow Metab 2015; 35: 86-94
31. Winkler EA, Sengillo JD, Sullivan JS, Henkel JS, Appel SH and Zlokovic BV. Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis. Acta Neuropathol 2013; 125: 111-120
32. Sagare AP, Bell RD, Zhao Z, Ma Q, Winkler EA, Ramanathan A, et al. Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat Commun 2013; 4: 2932
33. Park L, Zhou J, Zhou P, Pistick R, El Jamal S, Younkin L, et al. Innate immunity receptor CD36 promotes cerebral amyloid angiopathy. Proc Natl Acad Sci USA 2013; 110: 3089-3094
34. 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
35. 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
36. Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, et al. Clearance of Alzheimer's amyloidss( 1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 2000; 106: 1489-1499
37. Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP and Zhao Z. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 2015; 85: 296-302
38. Montagne A, Pa J and Zlokovic BV. Vascular plasticity and cognition during normal aging and dementia. JAMA Neurol2015; (in press)
39. Conejero-Goldberg C, Gomar JJ, Bobes-Bascaran T, Hyde TM, Kleinman JE, Herman MM, et al. APOE2 enhances neuroprotection against Alzheimer's disease through multiple molecular mechanisms. Mol Psychiatry 2014; 19: 1243-1250
40. Kreczmanski P, Schmidt-Kastner R, Heinsen H, Steinbusch HW, Hof PR and Schmitz C. Stereological studies of capillary length density in the frontal cortex of schizophrenics. Acta Neuropathol 2005; 109: 510-518.