High frequency of apolipoprotein E epsilon 2 allele is specific for patients with cerebral amyloid angiopathy-related haemorrhage.

The apolipoprotein E (APOE) epsilon 2 allele is a putative risk factor for cerebral amyloid angiopathy-related haemorrhage. We explored the frequency of the APOE epsilon 2 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 epsilon 2 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 epsilon 2 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 epsilon 2 allele is associated with haemorrhage only in the context of cerebral blood vessels laden with amyloid.