Zerebrale Amyloidangiopathie

Die zerebrale Amyloidangiopathie (CAA) ist eine Erkrankung, bei der sich beta-Amyloid in den Gefäßwänden des Gehirns ablagert. Sie ist eine bedeutende Ursache für lobäre Hirnblutungen und Demenz. Der Beitrag beleuchtet die Epidemiologie, Pathophysiologie und klinischen Erscheinungsbilder der CAA, einschließlich ihrer inflammatorischen Variante. Zudem werden neueste Erkenntnisse zur iatrogenen CAA und zu Amyloid-assoziierten Bildgebungsabnormalitäten (ARIA) im Zusammenhang mit neuen Alzheimer-Therapien vorgestellt.

Kernaussagen

• Die CAA ist durch Ablagerungen von beta-Amyloid in Gefäßwänden des Gehirns gekennzeichnet und eine Hauptursache für lobäre intrazerebrale Blutungen.

• Die Prävalenz einer moderaten CAA bei 84-Jährigen wird auf etwa 23% geschätzt, bei Alzheimer-Patienten liegt sie bei 50–80%.

• Die Pathophysiologie der CAA verläuft in 4 Stadien, von ersten Ablagerungen bis hin zu klinisch symptomatischen Hirnblutungen.

• Mikroblutungen und kortikale superfiziale Siderose sind charakteristische MRT-Merkmale der CAA.

• Es gibt zunehmende Evidenz für ein „prionenähnliches Verhalten“ von beta-Amyloid, was zu iatrogener CAA führen kann.

• ARIA treten bei 40% der Patienten unter Anti-Amyloid-Immuntherapien wie Aducanumab auf und erfordern spezielle Behandlungsstrategien.

• Die CAA-ri zeigt ähnliche Risikofaktoren wie ARIA, unterscheidet sich aber in Häufigkeit und Schwere der Symptome.

Publikationsverlauf

Artikel online veröffentlicht:
09. September 2024

• Literatur

• 1 Malhotra K, Theodorou A, Katsanos AH. et al. Prevalence of Clinical and Neuroimaging Markers in Cerebral Amyloid Angiopathy: A Systematic Review and Meta-Analysis. Stroke 2022; 53: 1944-1953 DOI: 10.1161/STROKEAHA.121.035836. (PMID: 35264008)
• 2 Charidimou A, Peeters A, Fox Z. et al. Spectrum of transient focal neurological episodes in cerebral amyloid angiopathy: multicentre magnetic resonance imaging cohort study and meta-analysis. Stroke 2012; 43: 2324-2330 DOI: 10.1161/STROKEAHA.112.657759. (PMID: 22798323)
• 3 Theodorou A, Palaiodimou L, Malhotra K. et al. Clinical Neuroimaging and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis. Stroke 2023; 54: 178-188 DOI: 10.1161/STROKEAHA.122.040671. (PMID: 36453271)
• 4 Jäkel L, De Kort AM, Klijn CJM. et al. Prevalence of cerebral amyloid angiopathy: A systematic review and meta-analysis. Alzheimers Dement 2022; 18: 10-28 DOI: 10.1002/alz.12366. (PMID: 34057813)
• 5 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
• 6 Koemans EA, Chhatwal JP, van Veluw SJ. et al. Progression of cerebral amyloid angiopathy: a pathophysiological framework. Lancet Neurol 2023; 22: 632-642 DOI: 10.1016/S1474-4422(23)00114-X. (PMID: 37236210)
• 7 Charidimou A, Smith EE. Cardiovascular Management in Asymptomatic (Silent) Cerebral Microbleeds and Suspected Cerebral Amyloid Angiopathy. Stroke 2024; 55: 1101-1112 DOI: 10.1161/STROKEAHA.123.044167. (PMID: 38465605)
• 8 Banerjee G, Farmer SF, Hyare H. et al. Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth hormone. Nat Med 2024; 30: 394-402 DOI: 10.1038/s41591-023-02729-2. (PMID: 38287166)
• 9 Greenberg SM. Blood Transfusion and Brain Amyloidosis: Should We Be Worried?. JAMA 2023; 330: 921-922 DOI: 10.1001/jama.2023.14522. (PMID: 37698576)
• 10 Zhao J, Rostgaard K, Lauwers E. et al. Intracerebral Hemorrhage Among Blood Donors and Their Transfusion Recipients. JAMA 2023; 330: 941-950
• 11 Doran SJ, Sawyer RP. Risk factors in developing amyloid related imaging abnormalities (ARIA) and clinical implications. Front Neurosci 2024; 18: 1326784 DOI: 10.3389/fnins.2024.1326784. (PMID: 38312931)
• 12 Kharal A, Amin M, Aboseif A. et al. Abstract TMP30: High Prevalence Of Unrecognized Cerebral Amyloid Angiopathy Related Inflammation Among Patients With Cerebral Amyloid Angiopathy And White Matter Disease. Stroke 2023; 54 (Suppl. 01) TMP30 DOI: 10.1161/str.54.suppl_1.TMP30.
• 13 Kinnecom C, Lev MH, Wendell L. et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology 2007; 68: 1411-1416 DOI: 10.1212/01.wnl.0000260066.98681.2e. (PMID: 17452586)
• 14 Auriel E, Charidimou A, Gurol ME. et al. Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation. JAMA Neurol 2016; 73: 197-202 DOI: 10.1001/jamaneurol.2015.4078. (PMID: 26720093)
• 15 Henneicke S, Neumann K, Kokott A. et al. Die inflammatorische Variante der CAA – ein Update. [im Druck]. Ärztl Prax Neurol Psychiatr 2025.
• 16 McNally JS, Sakata A, Alexander MD. et al. Vessel Wall Enhancement on Black-Blood MRI Predicts Acute and Future Stroke in Cerebral Amyloid Angiopathy. AJNR Am J Neuroradiol 2021; 42: 1038-1045 DOI: 10.3174/ajnr.A7047. (PMID: 33737266)
• 17 Charidimou A, Boulouis G, Frosch MP. et al. The Boston criteria version 2.0 for cerebral amyloid angiopathy: a multicentre retrospective MRI-neuropathology diagnostic accuracy study. Lancet Neurol 2022; 21: 714-725 DOI: 10.1016/S1474-4422(22)00208-3. (PMID: 35841910)
• 18 Greenberg SM, Charidimou A. Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria. Stroke 2018; 49: 491-497 DOI: 10.1161/STROKEAHA.117.016990. (PMID: 29335334)
• 19 Sembill JA, Knott M, Xu M. et al. Simplified Edinburgh CT Criteria for Identification of Lobar Intracerebral Hemorrhage Associated With Cerebral Amyloid Angiopathy. Neurology 2022; 98: e1997-e2004
• 20 Rodrigues MA, Samarasekera N, Lerpiniere C. et al. The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study. Lancet Neurol 2018; 17: 232-240 DOI: 10.1016/S1474-4422(18)30006-1. (PMID: 29331631)
• 21 Charidimou A, Friedrich JO, Greenberg SM. et al. Core cerebrospinal fluid biomarker profile in cerebral amyloid angiopathy: A mets-analysis. Neurology 2018; 90: e754-e762
• 22 Sembill JA, Lusse C, Linnerbauer M. et al. Cerebrospinal fluid biomarkers for cerebral amyloid angiopathy. Brain Commun 2023; 5: fcad159 DOI: 10.1093/braincomms/fcad159. (PMID: 37389304)
• 23 Rasing I, Voigt S, Koemans EA. et al. Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy. Alzheimers Res Ther 2024; 16: 86 DOI: 10.1186/s13195-024-01457-0. (PMID: 38654326)
• 24 Muir RT, Ismail Z, Black SE. et al. Comparative methods for quantifying plasma biomarkers in Alzheimer’s disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics. Alzheimers Dement 2024; 20: 1436-1458 DOI: 10.1002/alz.13510. (PMID: 37908054)
• 25 Nochlin D, Bird TD, Nemens EJ. et al. Amyloid angiopathy in a Volga German family with Alzheimer’s disease and a presenilin-2 mutation (N141I). Ann Neurol 1998; 43: 131-135
• 26 Biffi A. Main features of hereditary cerebral amyloid angiopathies: A systematic review. Cereb Circ Cogn Behav 2022; 3: 100124 DOI: 10.1016/j.cccb.2022.100124. (PMID: 36324420)
• 27 Yarlas A, Gertz MA, Dasgupta NR. et al. Burden of hereditary transthyretin amyloidosis on quality of life. Muscle Nerve 2019; 60: 169-175 DOI: 10.1002/mus.26515. (PMID: 31093980)
• 28 Greenberg SM, Rebeck GW, Vonsattel JP. et al. Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol 1995; 38: 254-259
• 29 Kozberg MG, Perosa V, Gurol ME. et al. A practical approach to the management of cerebral amyloid angiopathy. Int J Stroke 2021; 16: 356-369 DOI: 10.1177/1747493020974464. (PMID: 33252026)
• 30 Smith EE, Charidimou A, Ayata C. et al. Cerebral Amyloid Angiopathy-Related Transient Focal Neurologic Episodes. Neurology 2021; 97: 231-238 DOI: 10.1212/WNL.0000000000012234. (PMID: 34016709)
• 31 Charidimou A, Turc G, Oppenheim C. et al. Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis. Stroke 2017; 48: 2084-2090 DOI: 10.1161/STROKEAHA.116.012992. (PMID: 28720659)
• 32 Schlemm L, Braemswig TB, Boutitie F. et al. Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke. Neurology 2022; 98: e302-e314 DOI: 10.1212/WNL.0000000000013055. (PMID: 34782419)
• 33 Gattringer T, Eppinger S, Beitzke M. et al. Cortical Superficial Siderosis and Risk of Bleeding after Thrombolysis for Ischemic Stroke. Cerebrovasc Dis 2015; 40: 191-197 DOI: 10.1159/000439184. (PMID: 26351845)
• 34 Rosand J, Eckman MH, Knudsen KA. et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004; 164: 880-884 DOI: 10.1001/archinte.164.8.880. (PMID: 15111374)
• 35 Charidimou A, Boulouis G, Xiong L. et al. Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy. Neurology 2017; 88: 1607-1614 DOI: 10.1212/WNL.0000000000003866. (PMID: 28356458)
• 36 Al-Shahi Salman R, Minks DP, Mitra D. et al. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised open-label trial. Lancet Neurol 2019; 18: 643-652
• 37 Wilson D, Ambler G, Shakeshaft C. et al. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol 2018; 17: 539-547 DOI: 10.1016/S1474-4422(18)30145-5. (PMID: 29778365)
• 38 Smith EE, Saposnik G, Biessels GJ. et al. Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2017; 48: e44-e71
• 39 Charidimou A, Boulouis G, Greenberg SM. et al. Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy: A meta-analysis. Neurology 2019; 93: e2192-e2202 DOI: 10.1212/WNL.0000000000008590. (PMID: 31732564)
• 40 Eikelboom JW, O´Donnell M, Yusuf S. et al. Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment. Am Heart J 2010; 159: 348-353.e1 DOI: 10.1016/j.ahj.2009.08.026. (PMID: 20211294)
• 41 Steiner T, Unterberg A. S2k-Leitlinie: Behandlung von spontanen intrazerebralen Blutungen. DGNeurologie 2021; 4: 457-480
• 42 Li W, Jin C, Vaidya A. et al. Blood Pressure Trajectories and the Risk of Intracerebral Hemorrhage and Cerebral Infarction: A Prospective Study. Hypertension 2017; 70: 508-514 DOI: 10.1161/HYPERTENSIONAHA.117.09479. (PMID: 28716992)
• 43 Rothwell PM. Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Lancet 2010; 375: 938-948 DOI: 10.1016/S0140-6736(10)60309-1. (PMID: 20226991)
• 44 Sveikata L, Zanon Zotin NC, Schoemaker D. et al. Association of Long-Term Blood Pressure Variability with Cerebral Amyloid Angiopathy-related Brain Injury and Cognitive Decline. medRxiv 2024; DOI: 10.1101/2024.02.24.24303071.
• 45 Amarenco P, Bogousslavsky J, Callahan 3rd A. et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355: 549-559 DOI: 10.1056/NEJMoa061894. (PMID: 16899775)
• 46 Lioutas VA, Beiser AS, Aparicio HJ. et al. Assessment of Incidence and Risk Factors of Intracerebral Hemorrhage Among Participants in the Framingham Heart Study Between 1948 and 2016. JAMA Neurol 2020; 77: 1252-1260
• 47 Boe NJ, Hald SM, Jensen MM. et al. Association Between Statin Use and Intracerebral Hemorrhage Location: A Nested Case-Control Registry Study. Neurology 2023; 100: e1048-e1061