Apolipoprotein E ε4 Is Associated With the Presence and Earlier Onset of Hemorrhage in Cerebral Amyloid Angiopathy

Background and Purpose Cerebral amyloid angiopathy is an important cause of intracerebral hemorrhage in the elderly. The e4 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 ...

[1]  A. D. Roses,et al.  Association of apolipoprotein E allele €4 with late-onset familial and sporadic Alzheimer’s disease , 2006 .

[2]  P A Wolf,et al.  Apolipoprotein E alleles, dyslipidemia, and coronary heart disease. The Framingham Offspring Study. , 1994, JAMA.

[3]  B. Hyman,et al.  Apolipoprotein E and cognitive change in an elderly population , 1996, Annals of neurology.

[4]  B. Hyman,et al.  Apolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy , 1995 .

[5]  B T Hyman,et al.  Clinical and pathological correlates of apolipoprotein E ε4 in Alzheimer's disease , 1996, Annals of neurology.

[6]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[7]  R. Mahley,et al.  Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. , 1988, Science.

[8]  S. Finklestein,et al.  Petechial hemorrhages accompanying lobar hemorrhage , 1996, Neurology.

[9]  H. Vinters,et al.  Amyloid Angiopathy of Alzheimer's Disease: Amino Acid Composition and Partial Sequence of a 4,200‐Dalton Peptide Isolated from Cortical Microvessels , 1987, Journal of neurochemistry.

[10]  B. Hyman,et al.  Frequency of the apolipoprotein E ε2 allele is diminished in sporadic Alzheimer disease , 1994, Neuroscience Letters.

[11]  D. Graham,et al.  High frequency of apolipoprotein E ε2 in patients with cerebral hemorrhage due to cerebral amyloid angiopathy , 1996 .

[12]  A D Roses,et al.  Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[13]  B. Hyman,et al.  Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions , 1993, Neuron.

[14]  N. Craddock,et al.  Protection against Alzheimer's disease with apoE ∈2 , 1994, The Lancet.

[15]  R N Kalaria,et al.  Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. , 1996, The American journal of pathology.

[16]  B. Tycko,et al.  The apolipoprotein ε4 allele in patients with Alzheimer's disease , 1993, Annals of neurology.

[17]  T. Mandybur.  Cerebral Amyloid Angiopathy: The Vascular Pathology and Complications , 1986, Journal of neuropathology and experimental neurology.

[18]  K Kontula,et al.  Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. , 1995, The New England journal of medicine.

[19]  S. Atlas,et al.  Intracranial hemorrhage: gradient-echo MR imaging at 1.5 T. Comparison with spin-echo imaging and clinical applications. , 1988, Radiology.

[20]  D. Schaid,et al.  Apolipoprotein E: risk factor for Alzheimer disease. , 1994, American journal of human genetics.

[21]  J. Vonsattel,et al.  Cerebral amyloid angiopathy without and with cerebral hemorrhages: A comparative histological study , 1991, Annals of neurology.

[22]  H. Vinters.  Cerebral amyloid angiopathy. A critical review. , 1987, Stroke.

[23]  Steven M. Greenberg,et al.  Case 22-1996 , 1996 .

[24]  A. M. Saunders,et al.  Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease , 1994, Nature Genetics.

[25]  R. Scully,et al.  Case records of the Massachusetts General Hospital. , 1990 .

[26]  B. Frangione,et al.  Brain amyloid in normal aging and cerebral amyloid angiopathy is antigenically related to Alzheimer's disease beta-protein. , 1987, The American journal of pathology.