title: The distribution of cerebrovascular amyloid in Alzheimer's disease varies with ApoE genotype.
abstract: We performed a comparative study to assess cerebral amyloid angiopathy and ApoE genotype in cases of Alzheimer's disease (AD). Ten ApoE 3,3 and ten ApoE 4,4 AD brains, as well as ten normal control brains, were selected after matching for age, sex, and duration of disease. Sections of middle frontal and inferior parietal cortex including white matter sections were stained with an antibody against amyloid beta (Abeta), and extensive analysis of arteriolar Abeta deposition was performed using digital image analysis. Quantification of the staining revealed a larger cross-section of arteriolar walls occupied by Abeta in ApoE 4,4 and ApoE 3,3 AD subjects compared to controls. Our results show Abeta deposition in gray matter and white matter arterioles was predominantly found in ApoE 4,4 brains and, overall, Abeta deposition was greatest in these cases. This observation implies that there is greater vascular amyloid deposition (particularly in the white matter arterioles) in ApoE 4,4 AD individuals compared to ApoE 3,3 AD. These observations may give insight into the etiology behind the increased risk for AD associated with the ApoE-epsilon4 allele and the pathogenesis of vascular Abeta deposition.
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Trembath
authors.forename: John F
authors.initials: JF
authors.lastname: Ervin
authors.forename: Lucy
authors.initials: L
authors.lastname: Broom
authors.forename: Mari
authors.initials: M
authors.lastname: Szymanski
authors.forename: Kathleen
authors.initials: K
authors.lastname: Welsh-Bohmer
authors.forename: Carl
authors.initials: C
authors.lastname: Pieper
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hulette
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000097:blood*; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics*; D001808:Blood Vessels / Q000378:metabolism*; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D011180:Postmortem Changes
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E