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N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models.
J Alzheimers Dis 2016; 49(1):101-10JA

Abstract

According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid β-peptides (Aβs) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated Aβ variants is derived from the larger amyloid-β protein precursor (AβPP). Vast evidence suggests that Aβx-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Aβ peptides and Aβx-42 species appear to be the crucial players in AD etiology, the Aβ2-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of Aβ2-X in cases of AD and its distribution in AβPP/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using Aβ2-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular Aβ deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against Aβ-variants starting with the N-terminal Alanine-2.

Authors+Show Affiliations

Georg-August-University Göttingen, University Medicine Göttingen, Department of Psychiatry and Psychotherapy, Göttingen, Germany.Georg-August-University Göttingen, University Medicine Göttingen, Department of Psychiatry and Psychotherapy, Göttingen, Germany. LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.Moravian Biotechnology, Brno, Czech Republic.Georg-August-University Göttingen, University Medicine Göttingen, Department of Psychiatry and Psychotherapy, Göttingen, Germany.Georg-August-University Göttingen, University Medicine Göttingen, Department of Psychiatry and Psychotherapy, Göttingen, Germany.Georg-August-University Göttingen, University Medicine Göttingen, Department of Psychiatry and Psychotherapy, Göttingen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26529393

Citation

Savastano, Adriana, et al. "N-truncated Aβ2-X Starting With Position Two in Sporadic Alzheimer's Disease Cases and Two Alzheimer Mouse Models." Journal of Alzheimer's Disease : JAD, vol. 49, no. 1, 2016, pp. 101-10.
Savastano A, Klafki H, Hauβmann U, et al. N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models. J Alzheimers Dis. 2016;49(1):101-10.
Savastano, A., Klafki, H., Hauβmann, U., Oberstein, T. J., Muller, P., Wirths, O., ... Bayer, T. A. (2016). N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models. Journal of Alzheimer's Disease : JAD, 49(1), pp. 101-10. doi:10.3233/JAD-150394.
Savastano A, et al. N-truncated Aβ2-X Starting With Position Two in Sporadic Alzheimer's Disease Cases and Two Alzheimer Mouse Models. J Alzheimers Dis. 2016;49(1):101-10. PubMed PMID: 26529393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models. AU - Savastano,Adriana, AU - Klafki,Hans, AU - Hauβmann,Ute, AU - Oberstein,Timo Jan, AU - Muller,Petr, AU - Wirths,Oliver, AU - Wiltfang,Jens, AU - Bayer,Thomas A, PY - 2015/11/4/entrez PY - 2015/11/4/pubmed PY - 2016/9/20/medline KW - 5XFAD KW - Alzheimer’s disease KW - AβPP/PS1KI KW - N-truncated Aβ KW - immunohistochemistry KW - mouse model KW - postmortem SP - 101 EP - 10 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 49 IS - 1 N2 - According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid β-peptides (Aβs) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated Aβ variants is derived from the larger amyloid-β protein precursor (AβPP). Vast evidence suggests that Aβx-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Aβ peptides and Aβx-42 species appear to be the crucial players in AD etiology, the Aβ2-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of Aβ2-X in cases of AD and its distribution in AβPP/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using Aβ2-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular Aβ deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against Aβ-variants starting with the N-terminal Alanine-2. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/26529393/N_truncated_Aβ2_X_starting_with_position_two_in_sporadic_Alzheimer's_disease_cases_and_two_Alzheimer_mouse_models_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-150394 DB - PRIME DP - Unbound Medicine ER -