Human Pathology
Volume 41, Issue 11 , Pages 1601-1608 , November 2010

High-definition characterization of cerebral β-amyloid angiopathy in Alzheimer's disease

  • Virawudh Soontornniyomkij, MD

      Affiliations

    • Department of Pathology and Laboratory Medicine (Neuropathology), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
    • Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0603, USA
    • Corresponding Author InformationCorresponding author. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA.
  • ,
  • Cecilia Choi, MS

      Affiliations

    • Department of Pathology and Laboratory Medicine (Neuropathology), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
  • ,
  • Justine Pomakian, MPH

      Affiliations

    • Department of Pathology and Laboratory Medicine (Neuropathology), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
  • ,
  • Harry V. Vinters, MD

      Affiliations

    • Department of Pathology and Laboratory Medicine (Neuropathology), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
    • Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA

Received 4 February 2010 ,Revised 20 April 2010 ,Accepted 30 April 2010.

References 

  1. Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: the CERAD experience: Part XV. Neurology. 1996;46:1592–1596
  2. Weller RO, Subash M, Preston SD, Mazanti I, Carare RO. Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol. 2008;18:253–266
  3. Gearing M, Mori H, Mirra SS. Abeta-peptide length and apolipoprotein E genotype in Alzheimer's disease. Ann Neurol. 1996;39:395–399
  4. Mann DM, Iwatsubo T, Pickering-Brown SM, Owen F, Saido TC, Perry RH. Preferential deposition of amyloid beta protein (Abeta) in the form Abeta40 in Alzheimer's disease is associated with a gene dosage effect of the apolipoprotein E E4 allele. Neurosci Lett. 1997;221:81–84
  5. Alonzo NC, Hyman BT, Rebeck GW, Greenberg SM. Progression of cerebral amyloid angiopathy: accumulation of amyloid-beta40 in affected vessels. J Neuropathol Exp Neurol. 1998;57:353–359
  6. Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol. 2009;118:103–113
  7. Hawkes CA, McLaurin J. Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc Natl Acad Sci U S A. 2009;106:1261–1266
  8. Abbott NJ. Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int. 2004;45:545–552
  9. Carare RO, Bernardes-Silva M, Newman TA, et al. Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol. 2008;34:131–144
  10. Preston SD, Steart PV, Wilkinson A, Nicoll JA, Weller RO. Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol. 2003;29:106–117
  11. Attems J, Jellinger KA. Only cerebral capillary amyloid angiopathy correlates with Alzheimer pathology—a pilot study. Acta Neuropathol. 2004;107:83–90
  12. Thal DR, Ghebremedhin E, Rüb U, Yamaguchi H, Del Tredici K, Braak H. Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2002;61:282–293
  13. Stopa EG, Butala P, Salloway S, et al. Cerebral cortical arteriolar angiopathy, vascular beta-amyloid, smooth muscle actin, Braak stage, and APOE genotype. Stroke. 2008;39:814–821
  14. Singhrao S, Cole G, Henderson WJ, Newman GR. LR White embedding allows a multi-method approach to the analysis of brain tissue from patients with Alzheimer's disease. Histochem J. 1990;22:257–268
  15. Kumar-Singh S, Pirici D, McGowan E, et al. Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls. Am J Pathol. 2005;167:527–543
  16. Yamaguchi H, Yamazaki T, Lemere CA, Frosch MP, Selkoe DJ. Beta amyloid is focally deposited within the outer basement membrane in the amyloid angiopathy of Alzheimer's disease. An immunoelectron microscopic study. Am J Pathol. 1992;141:249–259
  17. Gearing M, Mirra SS, Hedreen JC, Sumi SM, Hansen LA, Heyman A. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer's disease. Neurology. 1995;45:461–466
  18. Soontornniyomkij V, Lynch MD, Mermash S, et al. Cerebral microinfarcts associated with severe cerebral beta-amyloid angiopathy. Brain Pathol. 2010;20:459–467
  19. Vinters HV, Vonsattel J. Neuropathologic features and grading of Alzheimer's related and sporadic CAA. In:  Verbeek MM,  de Waal RMW,  Vinters HV editor. Cerebral amyloid angiopathy in Alzheimer's disease and related disorders. Dordrecht, The Netherlands: Kluver Academic Publishers; 2000;p. 137–155
  20. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl). 1991;82:239–259
  21. Weller RO, Massey A, Newman TA, Hutchings M, Kuo YM, Roher AE. Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. Am J Pathol. 1998;153:725–733
  22. Haglund M, Kalaria R, Slade JY, Englund E. Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer's disease and vascular dementia. Acta Neuropathol (Berl). 2006;111:430–435
  23. Weller RO, Djuanda E, Yow HY, Carare RO. Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol. 2009;117:1–14
  24. Zhang ET, Inman CB, Weller RO. Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum. J Anat. 1990;170:111–123
  25. Mesulam M, Shaw P, Mash D, Weintraub S. Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Ann Neurol. 2004;55:815–828
  26. Farkas E, Luiten PG. Cerebral microvascular pathology in aging and Alzheimer's disease. Prog Neurobiol. 2001;64:575–611
  27. Roher AE, Kuo YM, Potter PE, et al. Cortical cholinergic denervation elicits vascular A beta deposition. Ann N Y Acad Sci. 2000;903:366–373
  28. Nicoll JA, Yamada M, Frackowiak J, Mazur-Kolecka B, Weller RO. Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer's disease. Pro-CAA position statement. Neurobiol Aging. 2004;25:589–597
  29. Kumar-Singh S, Cras P, Wang R, et al. Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric. Am J Pathol. 2002;161:507–520
  30. Miyakawa T, Kimura T, Hirata S, et al. Role of blood vessels in producing pathological changes in the brain with Alzheimer's disease. Ann N Y Acad Sci. 2000;903:46–54
  31. Kawai M, Cras P, Perry G. Serial reconstruction of beta-protein amyloid plaques: relationship to microvessels and size distribution. Brain Res. 1992;592:278–282
  32. Thal DR, Griffin WS, de Vos RA, Ghebremedhin E. Cerebral amyloid angiopathy and its relationship to Alzheimer's disease. Acta Neuropathol. 2008;115:599–609
  33. Sakai Y, Hosaka M, Hira Y, Watanabe T. Addition of phosphotungstic acid to ethanol for dehydration improves both the ultrastructure and antigenicity of pituitary tissue embedded in LR White acrylic resin. Arch Histol Cytol. 2005;68:337–347
  34. Vinters HV, Pardridge WM, Secor DL, Ishii N. Immunohistochemical study of cerebral amyloid angiopathy: II. Enhancement of immunostaining using formic acid pretreatment of tissue sections. Am J Pathol. 1988;133:150–162
  35. Armstrong RA, Lantos PL, Cairns NJ. Overlap between neurodegenerative disorders. Neuropathology. 2005;25:111–124

 This work was supported by the US National Institute on Aging grants P50 AG16570 and P01 AG12435, and the Dalijit S. & Elaine Sarkaria Chair in Diagnostic Medicine held by H.V.V., as well as an interdisciplinary research fellowship in neuroAIDS in the US National Institute of Health grant MH81482 to V.S.

☆☆ Disclosure: There are no real or potential conflicts of interest for any of the authors to disclose.

PII: S0046-8177(10)00161-9

doi: 10.1016/j.humpath.2010.04.011

Human Pathology
Volume 41, Issue 11 , Pages 1601-1608 , November 2010