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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.
Acta Neuropathol 2005; 110(5):459-71AN

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+Show Affiliations

Department of Neuropathology, University of Bonn, Sigmund Freud Str. 25, 53127 Bonn, Germany. dietmar.thal@uni-bonn.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16195918

Citation

Thal, Dietmar Rudolf, et al. "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." Acta Neuropathologica, vol. 110, no. 5, 2005, pp. 459-71.
Thal DR, Capetillo-Zarate E, Schultz C, et al. 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. Acta Neuropathol. 2005;110(5):459-71.
Thal, D. R., Capetillo-Zarate, E., Schultz, C., Rüb, U., Saido, T. C., Yamaguchi, H., ... Ghebremedhin, E. (2005). 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. Acta Neuropathologica, 110(5), pp. 459-71.
Thal DR, et al. 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. Acta Neuropathol. 2005;110(5):459-71. PubMed PMID: 16195918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Thal,Dietmar Rudolf, AU - Capetillo-Zarate,Estibaliz, AU - Schultz,Christian, AU - Rüb,Udo, AU - Saido,Takaomi C, AU - Yamaguchi,Haruyasu, AU - Haass,Christian, AU - Griffin,W Sue T, AU - Del Tredici,Kelly, AU - Braak,Heiko, AU - Ghebremedhin,Estifanos, Y1 - 2005/09/30/ PY - 2005/03/07/received PY - 2005/05/30/accepted PY - 2005/05/30/revised PY - 2005/10/1/pubmed PY - 2006/8/25/medline PY - 2005/10/1/entrez SP - 459 EP - 71 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 110 IS - 5 N2 - 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. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/16195918/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_ L2 - https://dx.doi.org/10.1007/s00401-005-1053-1 DB - PRIME DP - Unbound Medicine ER -