High frequency of apolipoprotein E ϵ2 allele is specific for patients with cerebral amyloid angiopathy-related haemorrhage

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Abstract

The apolipoprotein E (APOE) ϵ2 allele is a putative risk factor for cerebral amyloid angiopathy-related haemorrhage. We explored the frequency of the APOE ϵ2 allele in intracranial haemorrhage due to three different pathophysiological mechanisms to determine the specificity of the association. APOE genotypes in 207 autopsies with intracranial haemorrhage (96 subarachnoid haemorrhage, 71 deep intracerebral haemorrhage, 40 cerebral amyloid angiopathy (CAA)-related haemorrhage patients) were compared with 41 autopsy controls without neuropathological abnormalities and 406 living patients admitted to hospital following head injury. As identified previously the ϵ2 allele frequency was significantly over-represented in CAA-related haemorrhage (frequency 0.24, P<0.01); this association was stronger among patients with multiple CAA-related haematomas (0.31). The ϵ2 frequencies of the deep haemorrhage (0.13) and subarachnoid haemorrhage (0.09) groups were not significantly different from the control autopsies (0.07) or live patients (0.08). The findings indicate that the ϵ2 allele is associated with haemorrhage only in the context of cerebral blood vessels laden with amyloid.

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Acknowledgements

We wish to thank Professor D.I. Graham, Dr. D. Doyle, Dr. J.W. Ironside, Dr. H.V. Vinters, Professor S. Love and Dr. D.M.A. Mann for provision of case material, Professor G.M. Teasdale for permission to use head injury genotypes, and J. Stewart and K. Brown for assistance with genotyping. M.O.McC. is a Patrick Berthoud Research Fellow.

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