(Stroke. 1996;27:1333-1337.)
© 1996 American Heart Association, Inc.
Articles |
Apolipoprotein E 
4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy
the Departments of Neurology, Massachusetts General Hospital (S.M.G., M.E.B., B.T.H.), New England Medical Center (G.J.K., C.T., M.S.P.), Brigham and Women's Hospital (D.S.K.), and Boston University Medical Center (C.S.K.), Boston, Mass.
Background and Purpose Cerebral amyloid angiopathy is an important cause of intracerebral hemorrhage in the elderly. The 
4 allele of the apolipoprotein E gene, recently established as a genetic risk for Alzheimer's disease, has also been suggested as a possible risk factor for cerebral amyloid angiopathy. We sought to determine whether this allele is specifically associated with hemorrhages related to amyloid angiopathy and whether it correlates with the age at which first amyloid angiopathy-related hemorrhage occurs.
Methods Forty-five consecutive patients presenting with lobar hemorrhage were prospectively classified according to clinical, radiological, and when available, pathological features and evaluated for apolipoprotein E genotype. They were compared with 1899 elderly patients from a population-based sample and with 18 consecutive patients with hemorrhages in deep regions typical of a hypertensive mechanism.
Results Patients with multiple hemorrhages confined to the lobar territory demonstrated a greater than twofold overrepresentation (P<.001) in frequency of the apolipoprotein E 4 allele compared with the population-based sample. Apolipoprotein E genotypes of patients with hemorrhages in deep territories resembled the population sample. Among patients with strictly lobar hemorrhages, carriers of the 4 allele had their first hemorrhage more than 5 years earlier than noncarriers (mean age at first hemorrhage, 73.4±8.0 versus 78.9±7.4 years; P=.033). These effects were independent of the accompanying presence of Alzheimer's disease.
Conclusions The data support a specific role for apolipoprotein E 4 in accelerating the process that leads to amyloid angiopathy-related hemorrhage.
Key Words: amyloid • apolipoproteins • hemorrhage • risk factors
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|
|
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|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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