Apolipoprotein E co-localizes with newly formed amyloid β-protein (Aβ) deposits lacking immunoreactivity against N-terminal epitopes of Aβ in a genotype-dependent manner

Thal, Dietmar R., Capetillo-Zaratel, Estibaliz, Schultz, Christian, Rub, Udo, Saido. Takaomi, C., Yamaguchi, Haruyasu, Haass, Christian, Griffin, Sue T., Del Tredici, Kelly, Braak, Heiko and Ghebremedhin, Estifanos (2005) Apolipoprotein E co-localizes with newly formed amyloid β-protein (Aβ) deposits lacking immunoreactivity against N-terminal epitopes of Aβ in a genotype-dependent manner. Acta Neuropathologica, 110 5: 459-471.


Author Thal, Dietmar R.
Capetillo-Zaratel, Estibaliz
Schultz, Christian
Rub, Udo
Saido. Takaomi, C.
Yamaguchi, Haruyasu
Haass, Christian
Griffin, Sue T.
Del Tredici, Kelly
Braak, Heiko
Ghebremedhin, Estifanos
Title Apolipoprotein E co-localizes with newly formed amyloid β-protein (Aβ) deposits lacking immunoreactivity against N-terminal epitopes of Aβ in a genotype-dependent manner
Journal name Acta Neuropathologica   Check publisher's open access policy
ISSN 0001-6322
1432-0533
Publication date 2005-11
Sub-type Article (original research)
DOI 10.1007/s00401-005-1053-1
Volume 110
Issue 5
Start page 459
End page 471
Total pages 13
Place of publication Berlin, Germany
Publisher Springer
Language eng
Subject 110308 Geriatrics and Gerontology
110903 Central Nervous System
Abstract Different types of amyloid beta-protein (Abeta)-containing plaques occur in brains of Alzheimerrsquos 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 epsi4-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-Abeta42 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 epsi4/4 cases than in non-APOE epsi4/4 individuals, thereby underlining the potentially crucial role of apoE for the development of Abeta deposits.
Keyword Alzheimer's disease
Amyloid beta-protein
Apolipoprotein E
Amyloid plaque
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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