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01-09-2005 | Regular Paper

Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy

Authors: Johannes Attems, Kurt A. Jellinger, Felix Lintner

Published in: Acta Neuropathologica | Issue 3/2005

Abstract

Cerebral amyloid angiopathy (CAA) is defined by β-amyloid peptide (Aβ) depositions in cerebral vessels and is associated with Alzheimer’s disease (AD). The relationship between sporadic CAA and AD, and the origin of Aβ in CAA are poorly understood. The aim of our study was to investigate the relationship between CAA and AD. Autopsy brains (n=113, 61.1% female, 55.8% clinically demented, age range 54–102 years, mean ± SE 83.5±0.93 years) underwent standardized neuropathological assessment. CAA was evaluated in frontal, frontobasal, hippocampal, and occipital regions. Using immunohistochemistry, the severity of Aβ deposition in vessels was assessed semiquantitatively for each region separately. Evaluation of APOE genotype in 53 cases using real-time PCR showed significant correlations with severe AD pathology and CAA. CAA was present in 77 cases (68.1%), with the occipital region being affected significantly more often and more severely than other regions (P<0.01). Of brains without AD pathology 23.5% revealed CAA, whereas 24% with AD pathology showed no CAA. In concordance with other studies, the severity of both AD pathology and CAA showed a low, but significant correlation. This correlation, however, was only caused by the significant increase of occipital CAA with increasing AD pathology (P<0.01), and was independent of APOE genotype. Our results suggest that progressing AD pathology not only increases the severity of CAA, but also shifts its topographical distribution towards the occipital cortex.

Alonzo NC, Hyman BT, Rebeck GW, Greenberg SM (1998) Progression of cerebral amyloid angiopathy: accumulation of amyloid-beta40 in affected vessels. J Neuropathol Exp Neurol 57:353–359PubMed

Attems J, Jellinger KA (2004) Only cerebral capillary amyloid angiopathy correlates with Alzheimer pathology-a pilot study. Acta Neuropathol 107:83–90CrossRefPubMed

Attems J, Lintner F, Jellinger KA (2004) Amyloid beta peptide 1–42 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology. Acta Neuropathol 107:283–291CrossRefPubMed

Bergeron C, Ranalli PJ, Miceli PN (1987) Amyloid angiopathy in Alzheimer’s disease. Can J Neurol Sci 14:564–569PubMed

Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMed

Cadavid D, Mena H, Koeller K, Frommelt RA (2000) Cerebral beta amyloid angiopathy is a risk factor for cerebral ischemic infarction. A case control study in human brain biopsies. J Neuropathol Exp Neurol 59:768–773PubMed

Calhoun ME, Burgermeister P, Phinney AL, Stalder M, Tolnay M, Wiederhold KH, Abramowski D, Sturchler-Pierrat C, Sommer B, Staufenbiel M, Jucker M (1999) Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid. Proc Natl Acad Sci USA 96:14088–14093CrossRefPubMed

Chalmers K, Wilcock GK, Love S (2003) APOE epsilon 4 influences the pathological phenotype of Alzheimer’s disease by favouring cerebrovascular over parenchymal accumulation of A beta protein. Neuropathol Appl Neurobiol 29:231–238CrossRefPubMed

Delacourte A (2005) Alzheimer’s disease: a true tauopathy fueled by amyloid precursor protein dysfunction. In: Hanin I, Cacabelos R, Fisher A (eds) Recent advances in Alzheimer’s and Parkinson’s diseases. Taylor and Francis, London, pp 301–307

10.

Davis DG, Schmitt FA, Wekstein DR, Markesbery WR (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 58:376–388PubMed

11.

Dermaut B, Kumar-Singh S, De Jonghe C, Cruts M, Lofgren A, Lubke U, Cras P, Dom R, De Deyn PP, Martin JJ, Van Broeckhoven C (2001) Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer’s disease due to a novel presenilin 1 mutation. Brain 124:2383–2392CrossRefPubMed

12.

Ellis RJ, Olichney JM, Thal LJ, Mirra SS, Morris JC, Beekly D, Heyman A (1996) Cerebral amyloid angiopathy in the brains of patients with Alzheimer’s disease: the CERAD experience, Part XV. Neurology 46:1592–1596PubMed

13.

Fernando MS, Ince PG (2004) Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 226:13–17CrossRefPubMed

14.

Frackowiak J, Potempska A, LeVine H, Haske T, Dickson D, Mazur-Kolecka B (2005) Extracellular deposits of Abeta produced in cultures of Alzheimer disease brain vascular smooth muscle cells. J Neuropathol Exp Neurol 64:82–90PubMed

15.

Greenberg SM, Gurol ME, Rosand J, Smith EE (2004) Amyloid angiopathy-related vascular cognitive impairment. Stroke 35:2616–2619CrossRefPubMed

16.

Holton JL, Ghiso J, Lashley T, Rostagno A, Guerin CJ, Gibb G, Houlden H, Ayling H, Martinian L, Anderton BH, Wood NW, Vidal R, Plant G, Frangione B, Revesz T (2001) Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia. Am J Pathol 158:515–526PubMed

17.

Hyman BT (1998) New neuropathological criteria for Alzheimer disease. Arch Neurol 55:1174–1176CrossRefPubMed

18.

Jellinger KA (2002) Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm 109:813–836CrossRefPubMed

19.

Leclercq PD, Murray LS, Smith C, Graham DI, Nicoll JA, Gentleman SM (2005) Cerebral amyloid angiopathy in traumatic brain injury: association with apolipoprotein E genotype. J Neurol Neurosurg Psychiatry 76:229–233CrossRefPubMed

20.

Love S (2004) Contribution of cerebral amyloid angiopathy to Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75:1–4CrossRefPubMed

21.

Mackic JB, Weiss MH, Miao W, Kirkman E, Ghiso J, Calero M, Bading J, Frangione B, Zlokovic BV (1998) Cerebrovascular accumulation and increased blood-brain barrier permeability to circulating Alzheimer’s amyloid beta peptide in aged squirrel monkey with cerebral amyloid angiopathy. J Neurochem 70:210–215PubMed

22.

Mann DM, Pickering-Brown SM, Takeuchi A, Iwatsubo T (2001) Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer’s disease. Am J Pathol 158:2165–2175PubMed

23.

Maruyama K, Ikeda S, Ishihara T, Allsop D, Yanagisawa N (1990) Immunohistochemical characterization of cerebrovascular amyloid in 46 autopsied cases using antibodies to beta protein and cystatin C. Stroke 21:397–403PubMed

24.

Masuda J (1985) [Incidence of cerebral amyloid angiopathy in autopsy cases in Hisayama, Japan]. Jpn J Geriatr 22:138–143

25.

Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Belle G van, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486PubMed

26.

Mitchell TW, Mufson EJ, Schneider JA, Cochran EJ, Nissanov J, Han LY, Bienias JL, Lee VM, Trojanowski JQ, Bennett DA, Arnold SE (2002) Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer’s disease. Ann Neurol 51:182–189CrossRefPubMed

27.

Natte R, Vinters HV, Maat-Schieman ML, Bornebroek M, Haan J, Roos RA, Duinen SG van (1998) Microvasculopathy is associated with the number of cerebrovascular lesions in hereditary cerebral hemorrhage with amyloidosis, Dutch type. Stroke 29:1588–1594PubMed

28.

Natte R, Boer WI de, Maat-Schieman ML, Baelde HJ, Vinters HV, Roos RA, Duinen SG van (1999) Amyloid beta precursor protein-mRNA is expressed throughout cerebral vessel walls. Brain Res 828:179–183CrossRefPubMed

29.

Natte R, Yamaguchi H, Maat-Schieman ML, Prins FA, Neeskens P, Roos RA, Duinen SG van (1999) Ultrastructural evidence of early non-fibrillar Abeta42 in the capillary basement membrane of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type. Acta Neuropathol 98:577–582CrossRefPubMed

30.

Nicoll JA, Yamada M, Frackowiak J, Mazur-Kolecka B, Weller RO (2004) Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer’s disease; Pro-CAA position statement. Neurobiol Aging 25:589–597CrossRefPubMed

31.

Oide T, Takahashi H, Yutani C, Ishihara T, Ikeda S (2003) Relationship between lobar intracerebral hemorrhage and leukoencephalopathy associated with cerebral amyloid angiopathy: clinicopathological study of 64 Japanese patients. Amyloid 10:136–143PubMed

32.

Olichney JM, Hansen LA, Hofstetter CR, Grundman M, Katzman R, Thal LJ (1995) Cerebral infarction in Alzheimer’s disease is associated with severe amyloid angiopathy and hypertension. Arch Neurol 52:702–708PubMed

33.

Olichney JM, Ellis RJ, Katzman R, Sabbagh MN, Hansen L (1997) Types of cerebrovascular lesions associated with severe cerebral amyloid angiopathy in Alzheimer’s disease. Ann N Y Acad Sci 826:493–497PubMed

34.

Olichney JM, Hansen LA, Hofstetter CR, Lee JH, Katzman R, Thal LJ (2000) Association between severe cerebral amyloid angiopathy and cerebrovascular lesions in Alzheimer disease is not a spurious one attributable to apolipoprotein E4. Arch Neurol 57:869–874CrossRefPubMed

35.

Petrovitch H, White LR, Ross GW, Steinhorn SC, Li CY, Masaki KH, Davis DG, Nelson J, Hardman J, Curb JD, Blanchette PL, Launer LJ, Yano K, Markesbery WR (2001) Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study. Neurology 57:226–234PubMed

36.

Pfeifer LA, White LR, Ross GW, Petrovitch H, Launer LJ (2002) Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology 58:1629–1634PubMed

37.

Premkumar DR, Cohen DL, Hedera P, Friedland RP, Kalaria RN (1996) Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer’s disease. Am J Pathol 148:2083–2095PubMed

38.

Preston SD, Steart PV, Wilkinson A, Nicoll JA, Weller RO (2003) 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 29:106–117CrossRefPubMed

39.

Revesz T, Holton JL, Lashley T, Plant G, Rostagno A, Ghiso J, Frangione B (2002) Sporadic and familial cerebral amyloid angiopathies. Brain Pathol 12:343–357PubMed

40.

Revesz T, Ghiso J, Lashley T, Plant G, Rostagno A, Frangione B, Holton JL (2003) Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol 62:885–898PubMed

41.

Revesz T, Ghiso J, Plant G, Holton JL, Frangione B (2003) Inherited amyloidosis and neurodegenerations in familial British and Danish dementia. In: Dickson DW (ed) Neurodegeneration. The molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 380–385

42.

Riley KP, Snowdon DA, Markesbery WR (2002) Alzheimer’s neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol 51:567–577CrossRefPubMed

43.

Roher AE, Kuo YM, Esh C, Knebel C, Weiss N, Kalback W, Luehrs DC, Childress JL, Beach TG, Weller RO, Kokjohn TA (2003) Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer’s disease. Mol Med 9:112–122PubMed

44.

Rosenblum WI, Haider A (1988) Negative correlations between parenchymal amyloid and vascular amyloid in hippocampus. Am J Pathol 130:532–536PubMed

45.

Thal DR, Rub U, Orantes M, Braak H (2002) Phases of Abeta deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800PubMed

46.

Thal DR, Ghebremedhin E, Orantes M, Wiestler OD (2003) Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol 62:1287–1301PubMed

47.

Tian J, Shi J, Bailey K, Mann DM (2003) Negative association between amyloid plaques and cerebral amyloid angiopathy in Alzheimer’s disease. Neurosci Lett 352:137–140CrossRefPubMed

48.

Tian J, Shi J, Bailey K, Mann DM (2004) Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer’s disease. Neuropathol Appl Neurobiol 30:46–56CrossRefPubMed

49.

Tian J, Shi J, Mann DM (2004) Cerebral amyloid angiopathy and dementia. Panminerva Med 46:253–264PubMed

50.

Tomonaga M (1981) Cerebral amyloid angiopathy in the elderly. J Am Geriatr Soc 29:151–157PubMed

51.

Vidal R, Calero M, Piccardo P, Farlow MR, Unverzagt FW, Mendez E, Jimenez-Huete A, Beavis R, Gallo G, Gomez-Tortosa E, Ghiso J, Hyman BT, Frangione B, Ghetti B (2000) Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele. Acta Neuropathol 100:1–12CrossRefPubMed

52.

Vinters HV (1987) Cerebral amyloid angiopathy. A critical review. Stroke 18:311–324PubMed

53.

Vinters HV, Gilbert JJ (1983) Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke 14:924–928PubMed

54.

Vinters HV, Secor DL, Pardridge WM, Gray F (1990) Immunohistochemical study of cerebral amyloid angiopathy. III. Widespread Alzheimer A4 peptide in cerebral microvessel walls colocalizes with gamma trace in patients with leukoencephalopathy. Ann Neurol 28:34–42CrossRefPubMed

55.

Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson EP Jr (1991) Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 30:637–649CrossRefPubMed

56.

Weller RO, Nicoll JA (2003) Cerebral amyloid angiopathy: pathogenesis and effects on the ageing and Alzheimer brain. Neurol Res 25:611–616CrossRefPubMed

57.

Weller RO, Massey A, Newman TA, Hutchings M, Kuo YM, Roher AE (1998) Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer’s disease. Am J Pathol 153:725–733PubMed

58.

Weller RO, Massey A, Kuo YM, Roher AE (2000) Cerebral amyloid angiopathy: accumulation of A beta in interstitial fluid drainage pathways in Alzheimer’s disease. Ann N Y Acad Sci 903:110–117PubMed

59.

Williams S, Chalmers K, Wilcock GK, Love S (2005) Relationship between cerebral amyloid angiopathy and neurofibrillary pathology in Alzheimer’s disease. Neuropathol Appl Neurobiol 31:414–421CrossRefPubMed

60.

Wisniewski HM, Frackowiak J, Zoltowska A, Kim KS (1994) Vascular β-amyloid in Alzheimer’s disease angiopathy is produced by proliferating and degenerating smooth muscle cells. Int J Exp Clin Invest 41:8–16

61.

Xu D, Yang C, Wang L (2003) Cerebral amyloid angiopathy in aged Chinese: a clinico-neuropathological study. Acta Neuropathol 106:89–91PubMed

62.

Yamada M (2002) Risk factors for cerebral amyloid angiopathy in the elderly. Ann NY Acad Sci 977:37–44PubMed

63.

Yamada M, Tsukagoshi H, Otomo E, Hayakawa M (1987) Cerebral amyloid angiopathy in the aged. J Neurol 234:371–376CrossRefPubMed

64.

Yamashita M, Yamamoto T, Yamada M, Okino S, Fujita T (2002) [Sporadic cerebral amyloid angiopathy presenting with dementia and prominent capillary beta-amyloid deposition: a case report]. Rinsho Shinkeigaku 42:530–535PubMed

65.

Zekry D, Duyckaerts C, Belmin J, Geoffre C, Moulias R, Hauw JJ (2003) Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia. Acta Neuropathol (Berl) 106:367–373

66.

Zlokovic BV, Ghiso J, Mackic JB, McComb JG, Weiss MH, Frangione B (1993) Blood-brain barrier transport of circulating Alzheimer’s amyloid beta. Biochem Biophys Res Commun 197:1034–1040CrossRefPubMed

Title: Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy
Authors: Johannes Attems
Kurt A. Jellinger
Felix Lintner
Publication date: 01-09-2005
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 3/2005
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-005-1064-y

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Alzheimer’s disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy

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