Neurobiology of Aging
Volume 27, Issue 12 , Pages 1786-1796 , December 2006

Microvascular pathology in the aging human brain: Evidence that senile plaques are sites of microhaemorrhages

  • Karen M. Cullen

      Affiliations

    • Anatomy and Histology, School of Medical Sciences, Institute for Biomedical Research, The University of Sydney, Australia
    • Research School of Biological Sciences, Australian National University, Canberra, ACT, Australia
    • Corresponding Author InformationCorresponding author. Tel.: +61 2 9351 2696; fax: +61 2 9351 2813.
  • ,
  • Zoltán Kócsi

      Affiliations

    • Bendor Research Pty, Ltd, Sydney, NSW, Australia
  • ,
  • Jonathan Stone

      Affiliations

    • Research School of Biological Sciences, Australian National University, Canberra, ACT, Australia

Received 8 December 2004 ,Revised 13 October 2005 ,Accepted 18 October 2005.

References 

  1. Arriagada PV, Growden JH, Hedley-Whyte T, Hyman BT. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology. 1992;42:631–639
  2. Atwood CS, Bowen RL, Smith MA, Perry G. Cerebrovascular requirement for sealant, anti-coagulant and remodeling molecules that allow for the maintenance of vascular integrity and blood supply. Brain Res Rev. 2003;43(1):164–178
  3. Borroni B, Akkawi N, Martini G, Colciaghi F, Prometti P, Rozzini L, et al. Microvascular damage and platelet abnormalities in early Alzheimer's disease. J Neurol Sci. 2002;203–204:189–193
  4. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol (Berl). 1991;82:239–259
  5. Brown WR, Moody DM, Thore CR, Challa VR. Cerebrovascular pathology in Alzheimer's disease and leukoaraiosis. Ann N Y Acad Sci. 2000;903:39–45
  6. Buee L, Hof PR, Bouras C, Delacourte A, Perl DP, Morrison JH, et al. Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders. Acta Neuropathol (Berl). 1994;87(5):469–480
  7. Busciglio J, Gabuzda DH, Matsudaira P, Yankner BA. Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc Natl Acad Sci USA. 1993;50(5):2092–2096
  8. Bush AI, Martins RN, Rumble B, Moir R, Fuller S, Milward E, et al. The amyloid precursor protein of Alzheimer's disease is released by human platelets. J Biol Chem. 1990;265(26):15977–15983
  9. Bussiere T, Gold G, Kovari E, Giannakopoulos P, Bouras C, Perl DP, et al. Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer's disease. Neuroscience. 2003;117(3):577–592
  10. Chen M, Inestrosa NC, Ross GS, Fernandez HL. Platelets are the primary source of amyloid beta-peptide in human blood. Biochem Biophys Res Commun. 1995;213(1):96–103
  11. Chen XH, Siman R, Iwata A, Meaney DF, Trojanowski JQ, Smith DH. Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am J Pathol. 2004;165(2):357–371
  12. Coria F, Rubio I. Cerebral amyloid angiopathies. Neuropathol Appl Neurobiol. 1996;22:216–227
  13. Cullen KM. Perivascular astrocytes within Alzheimer's disease plaques. Neuroreport. 1997;8:1961–1966
  14. Cullen KM, Halliday GM. Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurobiol Aging. 1998;19:297–306
  15. Cullen KM, Kócsi Z, Stone J. Vascular relationships of haem-rich deposits in the aging cerebral cortex. J Cereb Blood Flow Metab. 2005;25(12):1656–1667
  16. D’Andrea MR, Cole GM, Ard MD. The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol Aging. 2004;25(5):675–683
  17. de la Torre J. Impaired cerebromicrovascular perfusion. Summary of evidence in support of its causality in Alzheimer's disease. Ann N Y Acad Sci. 2000;924:136–152
  18. De Meyer G, De Cleen D, Cooper S, Knaapen M, Jans D, Martinet W, et al. Platelet phagocytosis and processing of beta-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis. Circ Res. 2002;90(11):1197–1204
  19. Duyckaerts C, Bennecib M, Grignon Y, Uchihara T, He Y, Piette F, et al. Modeling the relation between neurofibrillary tangles and intellectual status. Neurobiol Aging. 1997;18(3):267–273
  20. Farkas E, De Vos RA, Jansen Steur EN, Luiten PG. Are Alzheimer's disease, hypertension, and cerebrocapillary damage related?. Neurobiol Aging. 2000;21(2):235–243
  21. Ferrer I, Boada Rovira M, Sanchez Guerra ML, Rey MJ, Costa-Jussa F. Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer's disease. Brain Pathol. 2004;14(1):11–20
  22. Frackowiak J, Mazur-Kolecka B, Wisniewski HM, Potempska A, Carroll RT, Emmerling MR, et al. Secretion and accumulation of Alzheimer's beta-protein by cultured vascular smooth muscle cells from old and young dogs. Brain Res. 1995;676(1):225–230
  23. 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(3):461–466
  24. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology. 2003;60(9):1495–1500
  25. Halliday GM, McCann HL, Pamphlett R, Brooks WS, Creasy H, McCusker E, et al. Brainstem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation. Acta Neuropathol (Berl). 1992;84:638–650
  26. Jellinger KA. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm. 2002;109(5–6):813–836
  27. Jellinger KA. The pathology of ischemic-vascular dementia: an update. J Neurol Sci. 2002;203–204:153–157
  28. Kalaria RN, Hedera P. Differential degeneration of the cerebral microvasculature in Alzheimer's disease. Neuroreport. 1995;6(3):477–480
  29. Kato T, Hirano A, Katagiri T, Sasaki H, Yamada S. Neurofibrillary tangle formation in the nucleus basalis of Meynert ipsilateral to a massive cerebral infarct. Ann Neurol. 1988;23:620–623
  30. Kawai M, Kalaria RN, Harik SI, Perry G. The relationship of amyloid plaques to cerebral capillaries in Alzheimer's disease. Am J Pathol. 1990;137(6):1435–1446
  31. Koeppen AH. The history of iron in the brain. J Neurol Sci. 1995;134S:1–9
  32. Kudo T, Imaizumi K, Tanimukai H, Katayama T, Sato N, Nakamura Y, et al. Are cerebrovascular factors involved in Alzheimer's disease?. Neurobiol Aging. 2000;21(2):215–224
  33. Lang IM, Moser KM, Schleef RR. Expression of Kunitz Protease Inhibitor containing forms of amyloid fl-protein precursor within vascular thrombi. Circulation. 1996;94(11):2728–2734
  34. Mari D, Parnetti L, Coppola R, Bottasso B, Reboldi G, Senin U, et al. Hemostasis abnormalities in patients with vascular dementia and Alzheimer's disease. Thromb Haemost. 1996;75(2):216–218
  35. Mayeux R, Tang MX, Jacobs DM, Manly J, Bell K, Merchant C, et al. Plasma amyloid beta-peptide 1–42 and incipient Alzheimer's disease. Ann Neurol. 1999;46(3):412–416
  36. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991;41(4):479–486
  37. Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989;39(9):1159–1165
  38. Nagele RG, Wegiel J, Venkataraman V, Imaki H, Wang KC. Contribution of glial cells to the development of amyloid plaques in Alzheimer's disease. Neurobiol Aging. 2004;25(5):663–674
  39. Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M, et al. Cerebral hemorrhage after passive anti-A-beta immunotherapy. Science. 2002;298:1379
  40. Racke MM, Boone LI, Hepburn DL, Parsadainian M, Bryan MT, Ness DK, et al. Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid. J Neurosci. 2005;25:629–636
  41. Regan RF, Rogers B. Delayed treatment of hemoglobin neurotoxicity. J Neurotrauma. 2003;20(1):111–120
  42. Reinhard JF, Liebmann JE, Schlosberg AJ, Moskowitz MA. Serotonin neurons project to small blood vessels in the brain. Science. 1979;206(4414):85–87
  43. Sato A, Sato Y, Uchida S. Regulation of regional cerebral blood flow by cholinergic fibers originating in the basal forebrain. Int J Dev Neurosci. 2001;19(3):327–337
  44. Schönheit B, Zarski R, Ohm TG. Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol Aging. 2004;25(6):697–711
  45. Shi J, Perry G, Smith MA, Friedland RP. Vascular abnormalities: the insidious pathogenesis of Alzheimer's disease. Neurobiol Aging. 2000;21(2):357–361
  46. Snowdon DA. Aging and Alzheimer's disease: lessons from the Nun Study. Gerontologist. 1997;37(2):150–156
  47. Su GC, Arendash GW, Kalaria RN, Bjugstad KB, Mullan M. Intravascular infusions of soluble beta-amyloid compromise the blood–brain barrier, activate CNS glial cells and induce peripheral hemorrhage. Brain Res. 1999;818:105–117
  48. Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, Breitner JC, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review. Neuroepidemiology. 2004;23(4):159–169
  49. Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, et al. Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol. 2002;161(5):1869–1879
  50. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M. β-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature. 1996;380:168–171
  51. van Dijk EJ, Prins ND, Vermeer SE, Koudstaal PJ, Breteler MM. Frequency of white matter lesions and silent lacunar infarcts. J Neural Transm Suppl. 2002;62:25–39
  52. Wagner K, Sharp F, Ardizzone T, Lu A, Clark J. Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab. 2003;23(6):629–652
  53. Wegiel J, Wisniewski HM, Muzylak M, Tarnawski M, Badmajew E, Nowakowski J, et al. Fibrillar amyloid-beta production, accumulation, and recycling in transgenic mice pancreatic acinar cells and macrophages. Amyloid. 2000;7(2):95–104
  54. Wisniewski HM, Wegiel J, Vorbrodt AW, Mazur-Kolecka B, Frackowiak J. Role of perivascular cells and myocytes in vascular amyloidosis. Ann N Y Acad Sci. 2000;903:6–18

PII: S0197-4580(05)00339-8

doi: 10.1016/j.neurobiolaging.2005.10.016

Neurobiology of Aging
Volume 27, Issue 12 , Pages 1786-1796 , December 2006