Download PDF
Semin Thromb Hemost 2013; 39(08): 955-962
DOI: 10.1055/s-0033-1357489
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Brain Hemorrhages in Cerebral Amyloid Angiopathy

Masahito Yamada
1   Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
09 October 2013 (online)

    Permissions and Reprints

Abstract

Cerebral amyloid angiopathy (CAA) is cerebrovascular amyloid deposition. It is classified into several types according to the cerebrovascular amyloid proteins involved. Sporadic amyloid β-protein (Aβ)-type CAA is commonly found in elderly individuals and patients with Alzheimer disease. CAA-related disorders include hemorrhagic and ischemic stroke and dementia. CAA-related hemorrhages include intracerebral lobar macrohemorrhages, cortical microhemorrhages, and focal subarachnoidal hemorrhages/superficial siderosis. CAA-associated vasculopathies, such as microaneurysmal formation with fibrinoid necrosis, underlie such cerebrovascular events. Sensitive magnetic resonance imaging procedures, such as gradient-echo T2* imaging and susceptibility-weighted images, are useful to detect microhemorrhagic lesions. Amyloid images with amyloid-binding positron emission tomography ligands can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. Hemorrhage-inducing factors for sporadic Aβ-type CAA include apolipoprotein E genotype, thrombolytic, anticoagulation, and antiplatelet therapies, hypertension, minor head trauma, and antiamyloid therapies. We need future strategies for protection of vessel walls against amyloid-related vascular damage, such as toxicity of Aβ oligomers, Aβ-induced oxidative stress, and inflammation, as well as development of antiamyloid therapies for CAA.

Keywords

cerebral amyloid angiopathy - intracerebral hemorrhage - cerebrovascular disorders - amyloid β-protein - risk factors
 

  • References

  • 1 Yamada M, Naiki H. Cerebral amyloid angiopathy. Prog Mol Biol Transl Sci 2012; 107 (7) 41-78
    PubMedGoogle Scholar
  • 2 Yamada M. Predicting cerebral amyloid angiopathy-related intracerebral hemorrhages and other cerebrovascular disorders in Alzheimer's disease. Front Neurol 2012; 3: 64
    PubMedGoogle Scholar
  • 3 Prelli F, Castaño E, Glenner GG, Frangione B. Differences between vascular and plaque core amyloid in Alzheimer's disease. J Neurochem 1988; 51 (2) 648-651
    CrossrefPubMedGoogle Scholar
  • 4 Suzuki N, Iwatsubo T, Odaka A, Ishibashi Y, Kitada C, Ihara Y. High tissue content of soluble β 1-40 is linked to cerebral amyloid angiopathy. Am J Pathol 1994; 145 (2) 452-460
    PubMedGoogle Scholar
  • 5 Samarasekera N, Smith C, Al-Shahi Salman R. The association between cerebral amyloid angiopathy and intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2012; 83 (3) 275-281
    CrossrefPubMedGoogle Scholar
  • 6 Yamada M, Tsukagoshi H, Otomo E, Hayakawa M. Cerebral amyloid angiopathy in the aged. J Neurol 1987; 234 (6) 371-376
    CrossrefPubMedGoogle Scholar
  • 7 Hirohata M, Yoshita M, Ishida C , et al. Clinical features of non-hypertensive lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Eur J Neurol 2010; 17 (6) 823-829
    CrossrefPubMedGoogle Scholar
  • 8 Meretoja A, Strbian D, Putaala J , et al. SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage. Stroke 2012; 43 (10) 2592-2597
    CrossrefPubMedGoogle Scholar
  • 9 Béjot Y, Cordonnier C, Durier J, Aboa-Eboulé C, Rouaud O, Giroud M. Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study. Brain 2013; 136 (Pt 2) 658-664
    CrossrefPubMedGoogle Scholar
  • 10 Itoh Y, Yamada M, Hayakawa M, Otomo E, Miyatake T. Cerebral amyloid angiopathy: a significant cause of cerebellar as well as lobar cerebral hemorrhage in the elderly. J Neurol Sci 1993; 116 (2) 135-141
    CrossrefPubMedGoogle Scholar
  • 11 Yamada M, Itoh Y, Otomo E, Hayakawa M, Miyatake T. Subarachnoid haemorrhage in the elderly: a necropsy study of the association with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry 1993; 56 (5) 543-547
    CrossrefPubMedGoogle Scholar
  • 12 Ohshima T, Endo T, Nukui H, Ikeda S, Allsop D, Onaya T. Cerebral amyloid angiopathy as a cause of subarachnoid hemorrhage. Stroke 1990; 21 (3) 480-483
    CrossrefPubMedGoogle Scholar
  • 13 Hanyu H, Tanaka Y, Shimizu S, Takasaki M, Abe K. Cerebral microbleeds in Alzheimer's disease. J Neurol 2003; 250 (12) 1496-1497
    CrossrefPubMedGoogle Scholar
  • 14 Nakata-Kudo Y, Mizuno T, Yamada K , et al. Microbleeds in Alzheimer disease are more related to cerebral amyloid angiopathy than cerebrovascular disease. Dement Geriatr Cogn Disord 2006; 22 (1) 8-14
    CrossrefPubMedGoogle Scholar
  • 15 Cordonnier C, van der Flier WM, Sluimer JD, Leys D, Barkhof F, Scheltens P. Prevalence and severity of microbleeds in a memory clinic setting. Neurology 2006; 66 (9) 1356-1360
    CrossrefPubMedGoogle Scholar
  • 16 Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007; 130 (Pt 8) 1988-2003
    CrossrefPubMedGoogle Scholar
  • 17 Pettersen JA, Sathiyamoorthy G, Gao FQ , et al. Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook dementia study. Arch Neurol 2008; 65 (6) 790-795
    CrossrefPubMedGoogle Scholar
  • 18 Brundel M, Heringa SM, de Bresser J , et al. High prevalence of cerebral microbleeds at 7Tesla MRI in patients with early Alzheimer's disease. J Alzheimers Dis 2012; 31 (2) 259-263
    PubMedGoogle Scholar
  • 19 Yates PA, Sirisriro R, Villemagne VL, Farquharson S, Masters CL, Rowe CC ; AIBL Research Group. Cerebral microhemorrhage and brain β-amyloid in aging and Alzheimer disease. Neurology 2011; 77 (1) 48-54
    CrossrefPubMedGoogle Scholar
  • 20 Dierksen GA, Skehan ME, Khan MA , et al. Spatial relation between microbleeds and amyloid deposits in amyloid angiopathy. Ann Neurol 2010; 68 (4) 545-548
    CrossrefPubMedGoogle Scholar
  • 21 Feldman HH, Maia LF, Mackenzie IR, Forster BB, Martzke J, Woolfenden A. Superficial siderosis: a potential diagnostic marker of cerebral amyloid angiopathy in Alzheimer disease. Stroke 2008; 39 (10) 2894-2897
    CrossrefPubMedGoogle Scholar
  • 22 Kumar S, Goddeau Jr RP, Selim MH , et al. Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies. Neurology 2010; 74 (11) 893-899
    CrossrefPubMedGoogle Scholar
  • 23 Linn J, Halpin A, Demaerel P , et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74 (17) 1346-1350
    CrossrefPubMedGoogle Scholar
  • 24 Vernooij MW, Ikram MA, Hofman A, Krestin GP, Breteler MM, van der Lugt A. Superficial siderosis in the general population. Neurology 2009; 73 (3) 202-205
    CrossrefPubMedGoogle Scholar
  • 25 Izenberg A, Aviv RI, Demaerschalk BM , et al. Crescendo transient Aura attacks: a transient ischemic attack mimic caused by focal subarachnoid hemorrhage. Stroke 2009; 40 (12) 3725-3729
    CrossrefPubMedGoogle Scholar
  • 26 Beitzke M, Gattringer T, Enzinger C, Wagner G, Niederkorn K, Fazekas F. Clinical presentation, etiology, and long-term prognosis in patients with nontraumatic convexal subarachnoid hemorrhage. Stroke 2011; 42 (11) 3055-3060
    CrossrefPubMedGoogle Scholar
  • 27 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 (9) 2324-2330
    CrossrefPubMedGoogle Scholar
  • 28 Linn J, Wollenweber FA, Lummel N , et al. Superficial siderosis is a warning sign for future intracranial hemorrhage. J Neurol 2013; 260 (1) 176-181
    CrossrefPubMedGoogle Scholar
  • 29 Zhu YC, Chabriat H, Godin O , et al. Distribution of white matter hyperintensity in cerebral hemorrhage and healthy aging. J Neurol 2012; 259 (3) 530-536
    CrossrefPubMedGoogle Scholar
  • 30 Kimberly WT, Gilson A, Rost NS , et al. Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy. Neurology 2009; 72 (14) 1230-1235
    CrossrefPubMedGoogle Scholar
  • 31 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 (Pt 8) 2376-2386
    CrossrefPubMedGoogle Scholar
  • 32 Yamada M, Itoh Y, Suematsu N, Otomo E, Matsushita M. Vascular variant of Alzheimer's disease characterized by severe plaque-like beta protein angiopathy. Dement Geriatr Cogn Disord 1997; 8 (3) 163-168
    CrossrefPubMedGoogle Scholar
  • 33 Cordonnier C, Leys D, Dumont F , et al. What are the causes of pre-existing dementia in patients with intracerebral haemorrhages?. Brain 2010; 133 (11) 3281-3289
    CrossrefPubMedGoogle Scholar
  • 34 Arvanitakis Z, Leurgans SE, Wang Z, Wilson RS, Bennett DA, Schneider JA. Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol 2011; 69 (2) 320-327
    CrossrefPubMedGoogle Scholar
  • 35 Oh U, Gupta R, Krakauer JW, Khandji AG, Chin SS, Elkind MS. Reversible leukoencephalopathy associated with cerebral amyloid angiopathy. Neurology 2004; 62 (3) 494-497
    CrossrefPubMedGoogle Scholar
  • 36 Eng JA, Frosch MP, Choi K, Rebeck GW, Greenberg SM. Clinical manifestations of cerebral amyloid angiopathy-related inflammation. Ann Neurol 2004; 55 (2) 250-256
    CrossrefPubMedGoogle Scholar
  • 37 Scolding NJ, Joseph F, Kirby PA , et al. Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy. Brain 2005; 128 (Pt 3) 500-515
    CrossrefPubMedGoogle Scholar
  • 38 Kinnecom C, Lev MH, Wendell L , et al. Course of cerebral amyloid angiopathy-related inflammation. Neurology 2007; 68 (17) 1411-1416
    CrossrefPubMedGoogle Scholar
  • 39 Nandigam RN, Viswanathan A, Delgado P , et al. MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength. AJNR Am J Neuroradiol 2009; 30 (2) 338-343
    PubMedGoogle Scholar
  • 40 Ii Y, Maeda M, Kida H , et al. In vivo detection of cortical microinfarcts on ultrahigh-field MRI. J Neuroimaging 2013; 23 (1) 28-32
    CrossrefPubMedGoogle Scholar
  • 41 Johnson KA, Gregas M, Becker JA , et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 2007; 62 (3) 229-234
    CrossrefPubMedGoogle Scholar
  • 42 Bacskai BJ, Frosch MP, Freeman SH , et al. Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Arch Neurol 2007; 64 (3) 431-434
    CrossrefPubMedGoogle Scholar
  • 43 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) 487-493
    CrossrefPubMedGoogle Scholar
  • 44 Gurol ME, Dierksen G, Betensky R , et al. Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy. Neurology 2012; 79 (4) 320-326
    CrossrefPubMedGoogle Scholar
  • 45 Verbeek MM, Kremer BP, Rikkert MO, Van Domburg PH, Skehan ME, Greenberg SM. Cerebrospinal fluid amyloid β(40) is decreased in cerebral amyloid angiopathy. Ann Neurol 2009; 66 (2) 245-249
    CrossrefPubMedGoogle Scholar
  • 46 Hernandez-Guillamon M, Delgado P, Penalba A , et al. Plasma β-amyloid levels in cerebral amyloid angiopathy-associated hemorrhagic stroke. Neurodegener Dis 2012; 10 (1-4) 320-323
    CrossrefPubMedGoogle Scholar
  • 47 Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001; 56 (4) 537-539
    CrossrefPubMedGoogle Scholar
  • 48 Greene GM, Godersky JC, Biller J, Hart MN, Adams Jr HP. Surgical experience with cerebral amyloid angiopathy. Stroke 1990; 21 (11) 1545-1549
    CrossrefPubMedGoogle Scholar
  • 49 Greenberg SM, Rebeck GW, Vonsattel JP, Gomez-Isla T, Hyman BT. Apolipoprotein E ε 4 and cerebral hemorrhage associated with amyloid angiopathy. Ann Neurol 1995; 38 (2) 254-259
    CrossrefPubMedGoogle Scholar
  • 50 Premkumar DR, Cohen DL, Hedera P, Friedland RP, Kalaria RN. Apolipoprotein E-ε4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. Am J Pathol 1996; 148 (6) 2083-2095
    PubMedGoogle Scholar
  • 51 Nicoll JA, Burnett C, Love S , et al. High frequency of apolipoprotein E ε 2 allele in hemorrhage due to cerebral amyloid angiopathy. Ann Neurol 1997; 41 (6) 716-721
    CrossrefPubMedGoogle Scholar
  • 52 Brouwers HB, Biffi A, McNamara KA , et al. Apolipoprotein E genotype is associated with CT angiography spot sign in lobar intracerebral hemorrhage. Stroke 2012; 43 (8) 2120-2125
    CrossrefPubMedGoogle Scholar
  • 53 O'Donnell HC, Rosand J, Knudsen KA , et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med 2000; 342 (4) 240-245
    CrossrefPubMedGoogle Scholar
  • 54 Thal DR, Ghebremedhin E, Rüb U, Yamaguchi H, Del Tredici K, Braak H. Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol 2002; 61 (3) 282-293
    PubMedGoogle Scholar
  • 55 Maxwell SS, Jackson CA, Paternoster L , et al. Genetic associations with brain microbleeds: Systematic review and meta-analyses. Neurology 2011; 77 (2) 158-167
    CrossrefPubMedGoogle Scholar
  • 56 Leclercq PD, Murray LS, Smith C, Graham DI, Nicoll JA, Gentleman SM. Cerebral amyloid angiopathy in traumatic brain injury: association with apolipoprotein E genotype. J Neurol Neurosurg Psychiatry 2005; 76 (2) 229-233
    CrossrefPubMedGoogle Scholar
  • 57 Hamaguchi T, Okino S, Sodeyama N , et al. Association of a polymorphism of the transforming growth factor-β1 gene with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry 2005; 76 (5) 696-699
    CrossrefPubMedGoogle Scholar
  • 58 Peila R, Yucesoy B, White LR , et al. A TGF-β1 polymorphism association with dementia and neuropathologies: the HAAS. Neurobiol Aging 2007; 28 (9) 1367-1373
    CrossrefPubMedGoogle Scholar
  • 59 Yamada M. Risk factors for cerebral amyloid angiopathy in the elderly. Ann N Y Acad Sci 2002; 977: 37-44
    CrossrefPubMedGoogle Scholar
  • 60 Yamada M. Cerebral amyloid angiopathy and gene polymorphisms. J Neurol Sci 2004; 226 (1-2) 41-44
    CrossrefPubMedGoogle Scholar
  • 61 Yamada M, Sodeyama N, Itoh Y , et al. Association of presenilin-1 polymorphism with cerebral amyloid angiopathy in the elderly. Stroke 1997; 28 (11) 2219-2221
    CrossrefPubMedGoogle Scholar
  • 62 Yamada M, Sodeyama N, Itoh Y , et al. Association of α1-antichymotrypsin polymorphism with cerebral amyloid angiopathy. Ann Neurol 1998; 44 (1) 129-131
    CrossrefPubMedGoogle Scholar
  • 63 Yamada M, Sodeyama N, Itoh Y , et al. Association of neprilysin polymorphism with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry 2003; 74 (6) 749-751
    CrossrefPubMedGoogle Scholar
  • 64 Christoforidis M, Schober R, Krohn K. Genetic-morphologic association study: association between the low density lipoprotein-receptor related protein (LRP) and cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2005; 31 (1) 11-19
    CrossrefPubMedGoogle Scholar
  • 65 Domingues-Montanari S, Hernandez-Guillamon M, Fernandez-Cadenas I , et al; Stroke Project Cerebrovascular Diseases Study Group, Spanish Society of Neurology. ACE variants and risk of intracerebral hemorrhage recurrence in amyloid angiopathy. Neurobiol Aging 2011; 32 (3) e13-e22
    PubMedGoogle Scholar
  • 66 Thal DR, Papassotiropoulos A, Saido TC , et al. Capillary cerebral amyloid angiopathy identifies a distinct APOE ε4-associated subtype of sporadic Alzheimer's disease. Acta Neuropathol 2010; 120 (2) 169-183
    CrossrefPubMedGoogle Scholar
  • 67 Biffi A, Shulman JM, Jagiella JM , et al. Genetic variation at CR1 increases risk of cerebral amyloid angiopathy. Neurology 2012; 78 (5) 334-341
    CrossrefPubMedGoogle Scholar
  • 68 Arima H, Tzourio C, Anderson C , et al; PROGRESS Collaborative Group. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke 2010; 41 (2) 394-396
    CrossrefPubMedGoogle Scholar
  • 69 Rosand J, Hylek EM, O'Donnell HC, Greenberg SM. Warfarin-associated hemorrhage and cerebral amyloid angiopathy: a genetic and pathologic study. Neurology 2000; 55 (7) 947-951
    CrossrefPubMedGoogle Scholar
  • 70 McCarron MO, Nicoll JA. Cerebral amyloid angiopathy and thrombolysis-related intracerebral haemorrhage. Lancet Neurol 2004; 3 (8) 484-492
    CrossrefPubMedGoogle Scholar
  • 71 Charidimou A, Kakar P, Fox Z, Werring DJ. Cerebral microbleeds and the risk of intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2013; 84 (3) 277-280
    CrossrefPubMedGoogle Scholar
  • 72 Charidimou A, Shakeshaft C, Werring DJ. Cerebral microbleeds on magnetic resonance imaging and anticoagulant-associated intracerebral hemorrhage risk. Front Neurol 2012; 3: 133
    PubMedGoogle Scholar
  • 73 Vernooij MW, Haag MD, van der Lugt A , et al. Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study. Arch Neurol 2009; 66 (6) 714-720
    CrossrefPubMedGoogle Scholar
  • 74 Thoonsen H, Richard E, Bentham P , et al. Aspirin in Alzheimer's disease: increased risk of intracerebral hemorrhage: cause for concern?. Stroke 2010; 41 (11) 2690-2692
    CrossrefPubMedGoogle Scholar
  • 75 Boche D, Zotova E, Weller RO , et al. Consequence of Abeta immunization on the vasculature of human Alzheimer's disease brain. Brain 2008; 131 (Pt 12) 3299-3310
    CrossrefPubMedGoogle Scholar
  • 76 Orgogozo JM, Gilman S, Dartigues JF , et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003; 61 (1) 46-54
    CrossrefPubMedGoogle Scholar
  • 77 Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 2003; 9 (4) 448-452
    CrossrefPubMedGoogle Scholar
  • 78 Sperling R, Salloway S, Brooks DJ , et al. Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol 2012; 11 (3) 241-249
    CrossrefPubMedGoogle Scholar
  • 79 Mandybur TI. Cerebral amyloid angiopathy: the vascular pathology and complications. J Neuropathol Exp Neurol 1986; 45 (1) 79-90
    CrossrefPubMedGoogle Scholar
  • 80 Vonsattel JP, Myers RH, Hedley-Whyte ET, Ropper AH, Bird ED, Richardson Jr EP. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 1991; 30 (5) 637-649
    CrossrefPubMedGoogle Scholar
  • 81 Maeda A, Yamada M, Itoh Y, Otomo E, Hayakawa M, Miyatake T. Computer-assisted three-dimensional image analysis of cerebral amyloid angiopathy. Stroke 1993; 24 (12) 1857-1864
    CrossrefPubMedGoogle Scholar
  • 82 Yamada M, Itoh Y, Shintaku M , et al. Immune reactions associated with cerebral amyloid angiopathy. Stroke 1996; 27 (7) 1155-1162
    CrossrefPubMedGoogle Scholar
  • 83 Revesz T, Holton JL, Lashley T , et al. Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol 2009; 118 (1) 115-130
    CrossrefPubMedGoogle Scholar
  • 84 Hernandez-Guillamon M, Martinez-Saez E, Delgado P , et al. MMP-2/MMP-9 plasma level and brain expression in cerebral amyloid angiopathy-associated hemorrhagic stroke. Brain Pathol 2012; 22 (2) 133-141
    CrossrefPubMedGoogle Scholar
  • 85 Lee JM, Yin K, Hsin I , et al. Matrix metalloproteinase-9 in cerebral-amyloid-angiopathy-related hemorrhage. J Neurol Sci 2005; 229-230: 249-254
    CrossrefPubMedGoogle Scholar
  • 86 McCarron MO, Nicoll JA, Stewart J , et al. The apolipoprotein E ε2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage. J Neuropathol Exp Neurol 1999; 58 (7) 711-718
    CrossrefPubMedGoogle Scholar
  • 87 Biffi A, Anderson CD, Jagiella JM , et al; International Stroke Genetics Consortium. APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study. Lancet Neurol 2011; 10 (8) 702-709
    CrossrefPubMedGoogle Scholar