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Vol. 8, No. 6, 2011
Issue release date: August 2011

Cerebral Amyloid Angiopathy, Blood-Brain Barrier Disruption and Amyloid Accumulation in SAMP8 Mice

del Valle J. · Duran-Vilaregut J. · Manich G. · Pallàs M. · Camins A. · Vilaplana J. · Pelegrí C.
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Abstract

Cerebrovascular dysfunction and β-amyloid peptide deposition on the walls of cerebral blood vessels might be an early event in the development of Alzheimer’s disease. Here we studied the time course of amyloid deposition in blood vessels and blood-brain barrier (BBB) disruption in the CA1 subzone of the hippocampus of SAMP8 mice and the association between these two variables. We also studied the association between the amyloid deposition in blood vessels and the recently described amyloid clusters in the parenchyma, as well as the association of these clusters with vessels in which the BBB is disrupted. SAMP8 mice showed greater amyloid deposition in blood vessels than age-matched ICR-CD1 control mice. Moreover, at 12 months of age the number of vessels with a disrupted BBB had increased in both strains, especially SAMP8 animals. At this age, all the vessels with amyloid deposition showed BBB disruption, but several capillaries with an altered BBB showed no amyloid on their walls. Moreover, amyloid clusters showed no spatial association with vessels with amyloid deposition, nor with vessels in which the BBB had been disrupted. Finally, we can conclude that vascular amyloid deposition seems to induce BBB alterations, but BBB disruption may also be due to other factors.



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References

  1. Alzheimer A: Über eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatrie Psych Gerichtl Med 1907;64:146–148.
  2. Kern A, Behl C: The unsolved relationship of brain aging and late-onset Alzheimer disease. Biochim Biophys Acta 2009;1790:1124–1132.
  3. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993;26:921–923.

    External Resources

  4. Bertram L, Tanzi RE: Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 2008;9:768–778.
  5. Williamson J, Goldman J, Marder KS: Genetic aspects of Alzheimer disease. Neurologist 2009;15:80–86.
  6. Götz J, Ittner LM: Animal models of Alzheimer’s disease and frontotemporal dementia. Nat Rev Neurosci 2008;9:532–544.
  7. Bryan KJ, Lee HG, Perry G, Smith MA, Casadesus G: Transgenic mouse models of Alzheimer’s disease: behavioral testing and considerations; in Buccafusco JJ (ed): Methods of Behavioral Analysis in Neuroscience, ed 2. Boca Raton, Taylor & Francis, 2009, pp 1–18.
  8. Tanzi RE, Bertram L: Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 2005;120:545–555.
  9. Van Dam D, De Deyn PP: Drug discovery in dementia: the role of rodent models. Nat Rev Drug Discov 2006;5:956–970.
  10. Morley JE, Banks WA, Kumar VB, Farr SA: The SAMP8 mouse as a model for Alzheimer disease: studies from Saint Louis University. Int Congr Ser 2004;1260:23–28.
  11. Del Valle J, Duran-Vilaregut J, Manich G, Casadesús G, Smith MA, Camins A, Pallàs M, Pelegrí C, Vilaplana J: Early amyloid accumulation in the hippocampus of SAMP8 mice. J Alzheimers Dis 2010;19:1303–1315.
  12. Hamamoto H, Honma A, Irino I, Matsushita T, Toda K, Matsumura M, Takeda T: Grading score system: a method for evaluation of the degree of senescence in senescence accelerated mouse (SAM). Mech Ageing Dev 1984;26:91–102.

    External Resources

  13. Takeda T, Hosokawa M, Higuchi K, Hosono M, Akiguchi I, Katoh H: A novel murine model of aging, senescence-accelerated mouse (SAM). Arch Gerontol Geriatr 1994;19:185–192.
  14. Nomura Y, Okuma Y: Age-related defects in lifespan and learning ability in SAMP8 mice. Neurobiol Aging 1999;20:111–115.
  15. Spangler EL, Patel N, Speer D, Hyman M, Hengemihle J, Markowska A, Ingram DK: Passive avoidance and complex maze learning in the senescence accelerated mouse (SAM): age and strain comparisons of SAM P8 and R1. J Gerontol A Biol Sci Med Sci 2002;57:B61–B68.

    External Resources

  16. Ueno M, Akiguchi I, Hosokawa M, Shinnou M, Sakamoto H, Takemura M, Higuchi K: Age-related changes in the brain transfer of blood-borne horseradish peroxidase in the hippocampus of senescence-accelerated mouse. Acta Neuropathol 1997;93:233–240.
  17. Onozuka M, Watanabe K, Fujita M, Tomida M, Ozono S: Changes in the septohippocampal cholinergic system following removal of molar teeth in the aged SAMP8 mouse. Behav Brain Res 2002;133:197–204.
  18. Flood JF, Farr SA, Uezu K, Morley JE: Age-related changes in septal serotonergic, GABAergic and glutamatergic facilitation of retention in SAMP8 mice. Mech Ageing Dev 1998;105:173–188.
  19. Kondziella D, Bidar A, Urfjell B, Sletvold O, Sonnewald U: The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: behavior and metabolism. Neurochem Int 2002;40:413–418.
  20. Nomura Y, Kitamura Y, Ohnuki T, Arima Y, Yamanaka Y, Sasaki K, Oonuma Y: Alterations in acetylcholine, NMDA, benzodiozepine receptors and protein kinase C in the brain of the senescence-accelerated mouse: an animal model useful for studies on cognitive enhancers. Behav Brain Res 1997;83:51–55.
  21. Takeda T: Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice. Neurochem Res 2009;34:639–659.
  22. Yagi H, Irino M, Matsushita T, Katoh S, Umezawa M, Tsuboyama T, Hosokawa M, Akiguchi I, Tokunaga R, Takeda T: Spontaneous spongy degeneration of the brain stem in SAM-P/8 mice, a newly developed memory-deficient strain. J Neuropathol Exp Neurol 1989;48:577–590.
  23. Kawamata T, Nakamura S, Akiguchi I: Dystrophic changes in axon accumulating nitric oxide synthase are accelerated with age in dorsal colime nuclei of senescence-accelerated mice (SAMP8); in Takeda T, et al (eds): The SAM Model of Senescence. Amsterdam, Elsevier Sciences BV, 1994, pp 347–350.
  24. Bartus RT, Dean RL, Beer B, Lippa AS: The cholinergic hypothesis of geriatric memory dysfunction. Science 1982;217:408–414.
  25. Francis PT, Palmer AM, Snape M, Wilcock GK: The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 1999;66:137–147.
  26. Hardy JA, Higgins GA: Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992;256:184–185.
  27. Rottkamp CA, Atwood CS, Joseph JA, Nunomura A, Perry G, Smith MA: The state versus amyloid-beta: the trial of the most wanted criminal in Alzheimer disease. Peptides 2002;23:1333–1341.
  28. Smith MA, Drew KL, Nunomura A, Takeda A, Hirai K, Zhu X, Atwood CS, Raina AK, Rottkamp CA, Sayre LM, Friedland RP, Perry G: Amyloid-beta, tau alterations and mitochondrial dysfunction in Alzheimer disease: the chickens or the eggs? Neurochem Int 2002;40:527–531.
  29. Mudher A, Lovestone S: Alzheimer’s disease – do tauists and baptists finally shake hands? Trends Neurosci 2002;25:22–26.
  30. Markesbery WR: Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 1997;23:134–147.
  31. Zhu X, Raina AK, Perry G, Smith MA: Alzheimer’s disease: the two-hit hypothesis. Lancet Neurol 2004;3:219–226.
  32. Scheibel AB, Duong TH, Jacobs R: Alzheimer’s disease as a capillary dementia. Ann Med 1989;21:103–107.
  33. Zlokovic BV: Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends Neurosci 2005;28:202–208.
  34. Banks WA, Farr SA, Morley JW: Permeability of the blood-brain barrier to albumin and insulin in the young and aged SAMP8 mouse. J Gerontol 2000;55A:B601–B606.
  35. Moinuddin A, Morley JE, Banks WA: Regional variations in the transport of interleukin-1 across the blood-brain barrier in ICR and aging SAMP8 mice. Neuroimmunomodulation 2000;8:165–170.
  36. Del Valle J, Duran-Vilaregut J, Manich G, Camins A, Pallàs M, Vilaplana J, Pelegrí C: Time-course of blood-brain barrier disruption in senescence-accelerated mouse prone 8 (SAMP8) mice. Int J Dev Neurosci 2009;27:47–52.
  37. Pelegrí C, Canudas AM, del Valle J, Casadesús G, Smith MA, Camins A, Pallàs M, Vilaplana J: Increased permeability of blood-brain barrier on the hippocampus of a murine model of senescence. Mech Ageing Dev 2007;128:522–528.
  38. Nonaka N, Banks WA, Mizushima H, Shioda S, Morley JE: Regional differences in PACAP transport across the blood-brain barrier in mice: a possible influence of strain, amyloid beta protein, and age. Peptides 2002;23:2197–2202.
  39. Hosokawa M, Ueno M: Aging of blood-brain barrier and neuronal cells of eye and ear in SAM mice. Neurobiol Aging 1999;20:117–123.
  40. Ueno M, Akiguchi I, Yagi H, Naiki H, Fujibayashi Y, Kimura J, Takeda T: Age-related changes in barrier function in mouse brain. I. Accelerated age-related increase of brain transfer of serum albumin in accelerated senescence prone SAM-P/8 mice with deficits in learning and memory. Arch Gerontol Geriatr 1993;16:233–248.
  41. Bell RD, Zlokovic BV: Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 2009;118:103–113.
  42. Greenberg SM, Gurol ME, Rosand J, Smith EE: Amyloid angiopathy-related vascular cognitive impairment. Stroke 2004;35;2616–2619.
  43. Jellinger KA: The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol 2007;113;349–388.
  44. Iadecola C: Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 2004;5:347–360.
  45. Paxinos G, Franklin KBJ: The Mouse Brain in Stereotaxic Coordinates. London, Academic Press, 2001.
  46. Attems J, Quass M, Jellinger KA, Lintner F: Topographical distribution of cerebral amyloid angiopathy and its effect on cognitive decline are influenced by Alzheimer disease pathology. J Neurol Sci 2007;257:49–55.
  47. Dickstein DL, Walsh J, Brautigam H, Stockton SD Jr, Gandy S, Hof PR: Role of vascular risk factors and vascular dysfunction in Alzheimer’s disease. Mt Sinai J Med 2010;77:82–102.
  48. Luck T, Riedel-Heller SG, Luppa M, Wiese B, Wollny A, Wagner M, Bickel H, Weyerer S, Pentzek M, Haller F, Moesch E, Werle J, Eisele M, Maier W, van den Bussche H, Kaduszkiewicz H, AgeCoDe Study Group: Risk factors for incident mild cognitive impairment – results from the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). Acta Psychiatr Scand 2010;121:260–272.
  49. Pallas M, Camins A, Smith MA, Perry G, Lee HG, Casadesus G: From aging to Alzheimer’s disease: unveiling ‘the switch’ with the senescence-accelerated mouse model (SAMP8). J Alzheimers Dis 2008;15:615–624.
  50. Abbott NJ, Rönnbäck L, Hansson E: Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006;7:41–53.
  51. Price JM, Hellermann A, Hellermann G, Sutton ET: Aging enhances vascular dysfunction induced by the Alzheimer’s peptide beta-amyloid. Neurol Res 2004;26:305–311.
  52. Vinters HV, Secor DL, Read SL, Frazee JG, Tomiyasu U, Stanley TM, Ferreiro JA, Akers MA: Microvasculature in brain biopsy specimens from patients with Alzheimer’s disease: an immunohistochemical and ultrastructural study. Ultrastruct Pathol 1994;18:333–348.
  53. Kumar-Singh S, Pirici D, McGowan E, Serneels S, Ceuterick C, Hardy J, Duff K, Dickson D, Van Broeckhoven C: 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.
  54. Kawai M, Kalaria RN, Harik SI, Perry G: The relationship of amyloid plaques to cerebral capillaries in Alzheimer’s disease. Am J Pathol 1990;137:1435–1446.
  55. Perry G, Smith MA, McCann CE, Siedlak SL, Jones PK, Friedland RP: Cerebrovascular muscle atrophy is a feature of Alzheimer’s disease. Brain Res 1998;791:63–66.
  56. Lippa CF, Hamos JE, Smith TW, Pulaski-Salo D, Drachman DA: Vascular amyloid deposition in Alzheimer’s disease: neither necessary nor sufficient for the local formation of plaques or tangles. Arch Neurol 1993;50:1088–1092.
  57. Nagababu E, Usatyuk PV, Enika D, Natarajan V, Rifkind JM: Vascular endothelial barrier dysfunction mediated by amyloid-beta proteins. J Alzheimers Dis 2009;17:845–854.
  58. Marlatt MW, Lucassen PJ, Perry G, Smith MA, Zhu X: Alzheimer’s disease: cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies. J Alzheimers Dis 2008;15:199–210.


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