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Neurology. 2015 Mar 24;84(12):1206-12. doi: 10.1212/WNL.0000000000001398. Epub 2015 Feb 25.

Cerebral amyloid angiopathy with and without hemorrhage: evidence for different disease phenotypes.

Author information

1
From the Department of Brain Repair and Rehabilitation (A.C.), UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; and the Hemorrhagic Stroke Research Program, Stroke Research Center, Department of Neurology (A.C., S.M.-R., A.S., J.O.-F., A. Vashkevich, A.A., J.R., M.E.G., S.M.G., A. Viswanathan), C.S. Kubik Laboratory for Neuropathology (M.F.), Division of Neurocritical Care and Emergency Neurology (J.R.), and Center for Human Genetic Research (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston. acharidimou@mgh.harvard.edu.
2
From the Department of Brain Repair and Rehabilitation (A.C.), UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK; and the Hemorrhagic Stroke Research Program, Stroke Research Center, Department of Neurology (A.C., S.M.-R., A.S., J.O.-F., A. Vashkevich, A.A., J.R., M.E.G., S.M.G., A. Viswanathan), C.S. Kubik Laboratory for Neuropathology (M.F.), Division of Neurocritical Care and Emergency Neurology (J.R.), and Center for Human Genetic Research (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.

Abstract

OBJECTIVE:

To gain insight into different cerebral amyloid angiopathy (CAA) phenotypes and mechanisms, we investigated cortical superficial siderosis (CSS), a new imaging marker of the disease, and its relation with APOE genotype in patients with pathologically proven CAA, who presented with and without intracerebral hemorrhage (ICH).

METHODS:

MRI scans of 105 patients with CAA pathologic confirmation and MRI were analyzed for CSS (focal, ≤3 sulci; disseminates, ≥4 sulci) and other imaging markers. We compared pathologic, imaging, and APOE genotype data between subjects with vs without ICH, and investigated associations between CSS and APOE genotype.

RESULTS:

Our cohort consisted of 54 patients with CAA with symptomatic lobar ICH and 51 without ICH. APOE genotype was available in 53 patients. More than 90% of pathology samples in both groups had neuritic plaques, whereas neurofibrillary tangles were more commonly present in the patients without ICH (87% vs 42%, p < 0.0001). There was a trend for patients with CAA with ICH to more commonly have APOE ε2 (48.7% vs 21.4%, p = 0.075), whereas patients without ICH were more likely to be APOE ε4 carriers (85.7% vs 53.9%, p = 0.035). Disseminated CSS was considerably commoner in patients with ICH (33.3% vs 5.9%, p < 0.0001). In logistic regression, disseminated CSS was associated with APOE ε2 (but not APOE ε4) (odds ratio 5.83; 95% confidence interval 1.49-22.82, p = 0.011).

CONCLUSIONS:

This neuropathologically defined CAA cohort suggests that CSS and APOE ε2 are related to the hemorrhagic expression of the disease; APOE ε4 is enriched in nonhemorrhagic CAA. Our study emphasizes the concept of different CAA phenotypes, suggesting divergent pathophysiologic mechanisms.

PMID:
25716356
PMCID:
PMC4366086
DOI:
10.1212/WNL.0000000000001398
[Indexed for MEDLINE]
Free PMC Article

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