title: Relationship between severe amyloid angiopathy, apolipoprotein E genotype, and vascular lesions in Alzheimer's disease.
abstract: In this brief review, we aim to describe the complex relationship between cerebral amyloid angiopathy (CAA), apolipoprotein E (ApoE), and cerebrovascular lesions in Alzheimer's disease (AD). First, we review the evidence that CAA is associated with, and may cause, specific types of vascular lesions (VLs). In addition to being a leading cause of lobar hemorrhages in the elderly, CAA has been implicated as a likely cause of small infarcts, microinfarcts, and incomplete infarctions in the deep white matter. We also review the role that ApoE4 (the major genetic risk factor for AD) has in predisposing toward CAA, coronary artery disease, and possibly toward cerebrovascular disease. Last, we provide evidence that the association between CAA and VLs is not a spurious one due to an increase in the ApoE4 genotype. Even within patient groups with the same ApoE genotype (specifically, E4/4 homozygotes and E3/3 homozygotes), our recent analyses have found significant increases in VLs in association with severe CAA. We discuss the implications of this finding as advancing a pathogenic role for severe CAA in producing many of the VLs commonly found in AD cases.
authors.affiliation: Alzheimer's Disease Research Center, University of California, San Diego, La Jolla, California 92093-0948, USA. olichney@cogsci.ucsd.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Olichney
authors.forename: L A
authors.initials: LA
authors.lastname: Hansen
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: C R
authors.initials: CR
authors.lastname: Hofstetter
authors.forename: R
authors.initials: R
authors.lastname: Katzman
authors.forename: L J
authors.initials: LJ
authors.lastname: Thal
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D002560:Cerebrovascular Circulation; D005838:Genotype; D006801:Humans
chemical_list: D001057:Apolipoproteins E