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Current Atherosclerosis Reports

01.08.2012 | Cardiovascular Disease and Stroke (M Fink and J Safdieh, Section Editors)

The Pathophysiology and Clinical Presentation of Cerebral Amyloid Angiopathy

verfasst von: Eitan Auriel, Steven Mark Greenberg

Erschienen in: Current Atherosclerosis Reports | Ausgabe 4/2012

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Abstract

Cerebral amyloid angiopathy (CAA) is defined as the deposition of amyloid ß peptide within leptomeningial and cortical vessels, likely reflecting an imbalance between Aβ production and clearance. Amyloid buildup triggers a series of destructive alterations in the cerebral vascular architecture, leading to a spectrum of neurological events including lobar intracerebral hemorrhage, brain ischemia and cognitive decline. Although traditionally diagnosed pathologically, neuroimaging has taken a central role in defining CAA. This review will discuss the pathological, clinical and radiological aspects of CAA.
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Literatur
1.
2.
Okazaki H, Reagan TJ, Campbell RJ. Clinicopathologic studies of primary cerebral amyloid angiopathy. Mayo Clin Proc. 1979;54(1):22–31.PubMed
3.
Pfeifer LA, White LR, Ross GW, et al. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology. 2002;58(11):1629–34.PubMedCrossRef
4.
Neuropathology Group. Medical Research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet. 2001;357(9251):169–75.CrossRef
5.
• Kimberly WT, Gilson A, Rost NS, et al. Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy. Neurology. 2009;72(14):1230–5. This recent study demonstrated that ICH, especially CAA related, predisposes to clinically silent cerebral microinfarction as well as intracerebral hemorrhage, suggesting that the lifetime burden of ischemic infarction in CAA could be substantial and might contribute to small vessel-related cognitive impairment. PubMedCrossRef
6.
• Gregoire SM, Charidimou A, Gadapa N, et al. Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study. Brain. 2011;134:2376–86. This recent study demonstrated that ICH, especially CAA related, predisposes to clinically silent cerebral microinfarction as well as intracerebral hemorrhage, suggesting that the lifetime burden of ischemic infarction in CAA could be substantial and might contribute to small vessel-related cognitive impairment. PubMedCrossRef
7.
• Prabhakaran S, Gupta R, Ouyang B, et al. Acute brain infarcts after spontaneous intracerebral hemorrhage: a diffusion-weighted imaging study. Stroke. 2010;41(1):89–94. This recent study demonstrated that ICH, especially CAA related, predisposes to clinically silent cerebral microinfarction as well as intracerebral hemorrhage, suggesting that the lifetime burden of ischemic infarction in CAA could be substantial and might contribute to small vessel-related cognitive impairment. PubMedCrossRef
8.
Jellinger KA. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm. 2002;109(5–6):813–36.PubMedCrossRef
9.
Herzig MC, Van Nostrand WE, Jucker M. Mechanism of cerebral beta-amyloid angiopathy: murine and cellular models. Brain Pathol. 2006;16(1):40–54.PubMedCrossRef
10.
Fukuchi K, Ho L, Younkin SG, et al. High levels of circulating beta-amyloid peptide do not cause cerebral beta-amyloidosis in transgenic mice. Am J Pathol. 1996;149(1):219–27.PubMed
11.
Burgermeister P, Calhoun ME, Winkler DT, Jucker M. Mechanisms of cerebrovascular amyloid deposition. Lessons from mouse models. Ann N Y Acad Sci. 2000;903:307–16.PubMedCrossRef
12.
Eisele YS, Obermüller U, Heilbronner G, et al. Peripherally applied Abeta-containing inoculates induce cerebral beta-amyloidosis. Science. 2010;330(6006):980–2.PubMedCrossRef
13.
Garcia-Alloza M, Gregory J, Kuchibhotla KV, et al. Cerebrovascular lesions induce transient β-amyloid deposition. Brain. 2011;134:3697–707.PubMedCrossRef
14.
Price DL, Tanzi RE, Borchelt DR, Sisodia SS. Alzheimer’s disease: genetic studies and transgenic models. Annu Rev Genet. 1998;32:461–93.PubMedCrossRef
15.
Greenberg SM, Nandigam RN, Delgado P, et al. Microbleeds versus macrobleeds: evidence for distinct entities. Stroke. 2009;40(7):2382–6.PubMedCrossRef
16.
Ishii K, Tamaoka A, Mizusawa H, et al. Abeta1-40 but not Abeta1-42 levels in cortex correlate with apolipoprotein E epsilon4 allele dosage in sporadic Alzheimer’s disease. Brain Res. 1997;748:250–2.PubMedCrossRef
17.
Love S, Miners S, Palmer J, et al. Insights into thepathogenesis and pathogenicity of cerebral amyloid angiopathy. Front Biosci. 2009;14:4778–92.PubMedCrossRef
18.
Masuda J, Tanaka K, Ueda K, Omae T. Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama, Japan. Stroke. 1988;19(2):205–10.PubMedCrossRef
19.
Vinters HV, Gilbert JJ. Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke. 1983;14(6):924–8.PubMedCrossRef
20.
Van Broeck B, Van Broeckhoven C, Kumar-Singh S. Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approaches. Neurodegener Dis. 2007;4(5):349–65.PubMedCrossRef
21.
Mandybur TI. Cerebral amyloid angiopathy: the vascular pathology and complications. J Neuropathol Exp Neurol. 1986;45(1):79–90.PubMedCrossRef
22.
Vonsattel JP, Myers RH, Hedley-Whyte ET, et al. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol. 1991;30:637–49.PubMedCrossRef
23.
Revesz T, Ghiso J, Lashley T, et al. Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. J Neuropathol Exp Neurol. 2003;62:885–98.PubMed
24.
Hartz AM, Bauer B, Soldner EL, et al. Amyloid-β contributes to blood–brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy. Stroke. 2012;43:514–23.PubMedCrossRef
25.
Puchtler H, Waldrop FS, Meloan SN. A review of light, polarization and fluorescence microscopic methods for amyloid. Appl Pathol. 1985;3:5–17.PubMed
26.
Maia LF, Mackenzie IR, Feldman HH. Clinical phenotypes of cerebral amyloid angiopathy. J Neurol Sci. 2007;257:23–30.PubMedCrossRef
27.
Qureshi AI, Tuhrim S, Broderick JP, et al. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344:1450–60.PubMedCrossRef
28.
Vinters HV, Wang ZZ, Secor DL. Brain parenchymal and microvascular amyloid in Alzheimer’s disease. Brain Pathol. 1996;6:179–95.PubMedCrossRef
29.
Winkler DT, Bondolfi L, Herzig MC, et al. Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy. J Neurosci. 2001;21:1619–27.PubMed
30.
Greenberg SM, Vonsattel JP, Stakes JW, et al. The clinical spectrum of cerebral amyloid angiopathy: presentations without lobar hemorrhage. Neurology. 1993;43:2073–9.PubMedCrossRef
31.
Yamada M, Itoh Y, Otomo E, et al. Subarachnoid haemorrhage in the elderly: a necropsy study of the association with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry. 1993;56:543–7.PubMedCrossRef
32.
Linn J, Herms J, Dichgans M, et al. Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol. 2008;29:184–6.PubMedCrossRef
33.
Finelli PF. Cerebral amyloid angiopathy as cause of convexity SAH in elderly. Neurologist. 2010;16:37–40.PubMedCrossRef
34.
Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology. 2010;74:1346–50.PubMedCrossRef
35.
Raposo N, Viguier A, Cuvinciuc V, et al. Cortical subarachnoid haemorrhage in the elderly: a recurrent event probably related to cerebral amyloid angiopathy. Eur J Neurol. 2011;18:597–603.PubMedCrossRef
36.
Greenberg SM, Rebeck GW, Vonsattel JP, et al. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol. 1995;38:254–9.PubMedCrossRef
37.
Premkumar DR, Cohen DL, Hedera P, et al. Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer’s disease. Am J Pathol. 1996;148:2083–95.PubMed
38.
McCarron MO, Nicoll JA, Ironside JW, et al. Cerebral amyloid angiopathy-related hemorrhage. Interaction of APOE epsilon2 with putative clinical risk factors. Stroke. 1999;30:1643–6.PubMedCrossRef
39.
Nicoll JA, Burnett C, Love S, et al. High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol. 1997;41:716–21.PubMedCrossRef
40.
McCarron MO, Nicoll JA, Ironside JW, et al. Cerebral amyloid angiopathy-related hemorrhage. Interaction of APOE epsilon2 with putative clinical risk factors. Stroke. 1999;30:1643–6.PubMedCrossRef
41.
Holtzman DM. Role of apoe/Abeta interactions in the pathogenesis of Alzheimer’s disease and cerebral amyloid angiopathy. J Mol Neurosci. 2001;17:147–55.PubMedCrossRef
42.
Rosand J, Hylek EM, O’Donnell HC, Greenberg SM. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology. 2000;55:947–51.PubMedCrossRef
43.
Eckman MH, Wong LK, Soo YO, et al. Patient-specific decision-making for warfarin therapy in nonvalvular atrial fibrillation: how will screening with genetics and imaging help? Stroke. 2008;39:3308–15.PubMedCrossRef
44.
Biffi A, Shulman JM, Jagiella JM, et al. Genetic variation at CR1 increases risk of cerebral amyloid angiopathy. Neurology. 2012;78:334–41.PubMedCrossRef
45.
• Arima H, Tzourio C, Anderson C, PROGRESS Collaborative Group, et al. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke. 2010;41:394–6. Currently there is no preventive strategy for CAA related ICH. In this subsidiary analysis of the PROGRESS trial routine blood pressure reduction was shown to protect patients with CAA from ICH. PubMedCrossRef
46.
Salloway S, Sperling R, Gilman S, et al. Bapineuzumab 201 Clinical Trial Investigators. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate. Alzheimer disease. Neurology. 2009;73:2061–70.PubMedCrossRef
47.
Bayer AJ, Bullock R, Jones RW, et al. Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN1792) in patients with AD. Neurology. 2005;64:94–101.PubMedCrossRef
48.
Biffi A, Greenberg SM. Cerebral amyloid angiopathy: a systematic review. J Clin Neurol. 2011;7:1–9.PubMedCrossRef
49.
Eckman MH, Rosand J, Knudsen KA, et al. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003;34:1710–6.PubMedCrossRef
50.
Biffi A, Halpin A, Towfighi A, et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010;75:693–8.PubMedCrossRef
51.
Fisher M, Vasilevko V, Passos GF, et al. Therapeutic modulation of cerebral microhemorrhage in a mouse model of cerebral amyloid angiopathy. Stroke. 2011;42:3300–3.PubMedCrossRef
52.
Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology. 2001;56:537–9.PubMedCrossRef
53.
Greenberg SM, Vernooij MW, Cordonnier C, Microbleed Study Group, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8(2):165–74.PubMedCrossRef
54.
Greenberg SM, Eng JA, Ning M, et al. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke. 2004;35:1415–20.PubMedCrossRef
55.
Rosand J, Muzikansky A, Kumar A, et al. Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy. Ann Neurol. 2005;58:459–62.PubMedCrossRef
56.
Mesker DJ, Poels MM, Ikram MA, et al. Lobar distribution of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol. 2011;68:656–9.PubMedCrossRef
57.
Smith EE, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Curr Atheroscler Rep. 2003;5:260–6.PubMedCrossRef
58.
Vernooij MW, Ikram MA, Hofman A, et al. Superficial siderosis in the general population. Neurology. 2009;73:202–5.PubMedCrossRef
59.
Klohs J, Deistung A, Schweser F, et al. Detection of cerebral microbleeds with quantitative susceptibility mapping in the ArcAbeta mouse model of cerebral amyloidosis. J Cereb Blood Flow Metab. 2011;31:2282–92.PubMedCrossRef
60.
Schrag M, McAuley G, Pomakian J, et al. Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study. Acta Neuropathol. 2010;119:291–302.PubMedCrossRef
61.
Johnson KA, Gregas M, Becker JA, et al. Imaging of amyloid burden and distribution in cerebral amyloidangiopathy. Ann Neurol. 2007;62:229–34.PubMedCrossRef
62.
Ly JV, Donnan GA, Villemagne VL, et al. 11C-PIB binding is increased in patients with cerebral amyloid angiopathy-related hemorrhage. Neurology. 2010;74(6):487–93.PubMedCrossRef
63.
Smith EE, Vijayappa M, Lima F, et al. Impaired visual evoked flow velocity response in cerebral amyloid angiopathy. Neurology. 2008;71:1424–30.PubMedCrossRef
64.
Thomas T, Thomas G, McLendon C, et al. beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature. 1996;380:168–71.PubMedCrossRef
65.
Christie R, Yamada M, Moskowitz M, Hyman B. Structural and functional disruption of vascular smooth muscle cells in a transgenic mouse model of amyloid angiopathy. Am J Pathol. 2001;158:1065–71.PubMedCrossRef
66.
Smith EE, Gurol ME, Eng JA, et al. White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage. Neurology. 2004;63:1606–12.PubMedCrossRef
67.
Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689–701.PubMedCrossRef
68.
Natté R, Maat-Schieman ML, Haan J, et al. Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type is associated with cerebral amyloid angiopathy but is independent of plaques and neurofibrillary tangles. Ann Neurol. 2001;50:765–72.PubMedCrossRef
69.
Gorelick PB, Scuteri A, Black SE, American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:2672–713.PubMedCrossRef
70.
Werring DJ, Gregoire SM, Cipolotti L. Cerebral microbleeds and vascular cognitive impairment. J Neurol Sci. 2010;299:131–5.PubMedCrossRef
71.
Holland CM, Smith EE, Csapo I, et al. Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging. Stroke. 2008;39:1127–33.PubMedCrossRef
72.
Soontornniyomkij V, Lynch MD, Mermash S, et al. Cerebral microinfarcts associated with severe cerebral beta-amyloid angiopathy. Brain Pathol. 2010;20:459–67.PubMedCrossRef
73.
Viswanathan A, Patel P, Rahman R, et al. Tissue microstructural changes are independently associated with cognitive impairment in cerebral amyloid angiopathy. Stroke. 2008;39:1988–92.PubMedCrossRef
74.
• Arvanitakis Z, Leurgans SE, Wang Z, et al. Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol. 2011;69:320–7. This is an up to date clinical-pathologic study of more than 400 older persons showing that CAA is very common in the demented and the non-demented population and is associated with AD, and after controlling for AD, with decline in specific cognitive performances. PubMedCrossRef
75.
Palsdottir A, Snorradottir AO, Thorsteinsson L. Hereditary cystatin C amyloid angiopathy: genetic, clinical, and pathological aspects. Brain Pathol. 2006;16:55–9.PubMedCrossRef
76.
Roks G, Van Harskamp F, De Koning I, et al. Presentation of amyloidosis in carriers of the codon 692 mutation in the amyloid precursor protein gene (APP692). Brain. 2000;123:2130–40.PubMedCrossRef
77.
Vidal R, Frangione B, Rostagno A, et al. A stop-codon mutation in the BRI gene associated with familial British dementia. Nature. 1999;399:776–81.PubMedCrossRef
78.
Vidal R, Garzuly F, Budka H, et al. Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G). Am J Pathol. 1996;148:361–6.PubMed
79.
Zhang-Nunes SX, Maat-Schieman ML, van Duinen SG, et al. The cerebral beta-amyloid angiopathies: hereditary and sporadic. Brain Pathol. 2006;16:30–9.PubMedCrossRef
80.
Greenberg SM, Shin Y, Grabowski TJ, et al. Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation. Neurology. 2003;60:1020–2.PubMedCrossRef
81.
Fountain NB, Eberhard DA. Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy: report of two cases and review of the literature. Neurology. 1996;46:190–7.PubMedCrossRef
82.
Eng JA, Frosch MP, Choi K, et al. Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol. 2004;55:250–6.PubMedCrossRef
83.
Kinnecom C, Lev MH, Wendell L, et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology. 2007;68:1411–6.PubMedCrossRef
84.
Kloppenborg RP, Richard E, Sprengers ME, et al. Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for immunosuppressive treatment. J Neuroinflammation. 2010;7:18.PubMedCrossRef
85.
• DiFrancesco JC, Brioschi M, Brighina L, et al. Anti-Aβ autoantibodies in the CSF of a patient with CAA-related inflammation: a case report. Neurology. 2011;76:842–4. This case report demonstrated for the first time that CSF anti-Aβ antibodies might serve as a biological marker for the diagnosis, monitoring and evaluation of treatment in CAA-related inflammation. PubMedCrossRef
86.
Greenberg SM, Frosch MP. Life imitates art: anti-amyloid antibodies and inflammatory cerebral amyloid angiopathy. Neurology. 2011;76:772–3.PubMedCrossRef
Metadaten
Titel
The Pathophysiology and Clinical Presentation of Cerebral Amyloid Angiopathy
verfasst von
Eitan Auriel
Steven Mark Greenberg
Publikationsdatum
01.08.2012
Verlag
Current Science Inc.
Erschienen in
Current Atherosclerosis Reports / Ausgabe 4/2012
Print ISSN: 1523-3804
Elektronische ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-012-0254-z

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