title: Apolipoprotein E co-localizes with newly formed amyloid beta-protein (Abeta) deposits lacking immunoreactivity against N-terminal epitopes of Abeta in a genotype-dependent manner.
abstract: Different types of amyloid beta-protein (Abeta)-containing plaques occur in brains of Alzheimer's disease (AD) patients. Diffuse plaques seen during early stages of AD differ from neuritic plaques in later stages both with respect to the length of the Abeta peptides and the presence of other proteins, e.g., apolipoprotein-E (apoE). Since apoE is involved in Abeta transport and clearance, and the epsilon4-allele of the apolipoprotein-E gene (APOE) is a major risk factor for sporadic AD, it is plausible to speculate that apoE plays a pathophysiological role in the initiation of Abeta deposition. To address the issue of whether binding of apoE to Abeta is involved in initial Abeta deposition, we studied the human medial temporal lobe of 60 autopsy cases encompassing the full spectrum of AD-related pathology. In temporal lobe regions, which become involved for the first time at a given stage of beta-amyloidosis, all plaques represent newly formed plaques, and these were studied with immunohistochemical methods. ApoE was present in 36 cases, and was frequently co-localized with newly formed Abeta deposits detectable with anti-Abeta(42) but not with antibodies raised against N-terminal epitopes of Abeta. In 10 additional cases, immunoreactivity against apoE was completely lacking in newly formed plaques, which, at the same time, displayed immunoreactivity against N-terminal epitopes of Abeta. The failure of N-terminal epitopes of Abeta to co-localize with apoE in newly formed plaques indicates that these deposits presumably contain apoE-Abeta complexes, in which the N-terminal epitopes of Abeta are often concealed after complexing with apoE, thus preventing subsequent binding of antibodies. Moreover, apoE-positive newly formed plaques were seen more frequently in APOE epsilon4/4 cases than in non-APOE epsilon4/4 individuals, thereby underlining the potentially crucial role of apoE for the development of Abeta deposits.
authors.affiliation: Department of Neuropathology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany. dietmar.thal@uni-bonn.de
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Capetillo-Zarate
authors.forename: Christian
authors.initials: C
authors.lastname: Schultz
authors.forename: Udo
authors.initials: U
authors.lastname: Rüb
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.forename: W Sue T
authors.initials: WS
authors.lastname: Griffin
authors.forename: Kelly
authors.initials: K
authors.lastname: Del Tredici
authors.forename: Heiko
authors.initials: H
authors.lastname: Braak
authors.forename: Estifanos
authors.initials: E
authors.lastname: Ghebremedhin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000276:immunology* / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000032:analysis* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D012307:Risk Factors; D013702:Temporal Lobe / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D000939:Epitopes