Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy.
Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular deposition of the amyloid beta-peptide, leading to intracerebral hemorrhage in severe cases. Other than rare familial cases, the only identified risks for CAA are advancing age and accompanying Alzheimer's disease. We tested whether the apolipoprotein E epsilon 4 (apoE epsilon 4) allele was associated with CAA and hemorrhage and whether this association was independent of Alzheimer's disease. The apoE epsilon 4 genotype was determined without knowledge of the pathology for 93 postmortem cases systematically graded for severity of CAA and for 15 patients with CAA-associated intracerebral hemorrhage. We found a significant and independent effect of the apoE genotype in both cohorts. Among the postmortem cases, the presence of apoE epsilon 4 increased the odds ratio for moderate or severe CAA by 2.9-fold, relative to cases without epsilon 4; two copies of epsilon 4 increased the odds ratio 13.1-fold. In the cohort of CAA-associated cerebral hemorrhages, the apoE epsilon 4 allele frequency was 0.40, significantly greater than the control frequency of 0.14. The increase in CAA remained even after controlling for the presence of Alzheimer's disease, suggesting that apoE epsilon 4 is a risk factor for CAA and CAA-related hemorrhage, independent of its association with Alzheimer's disease.
Greenberg
S M
SM
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Rebeck
G W
GW
Vonsattel
J P
JP
Gomez-Isla
T
T
Hyman
B T
BT
D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D003704:Dementia / Q000473:pathology; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data
D053327:Apolipoprotein E4; D001057:Apolipoproteins E