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N-truncated Aβ4-x peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models.
Alzheimers Res Ther 2017; 9(1):80AR

Abstract

BACKGROUND

The deposition of neurotoxic amyloid-β (Aβ) peptides in plaques in the brain parenchyma and in cerebral blood vessels is considered to be a key event in Alzheimer's disease (AD) pathogenesis. Although the presence and impact of full-length Aβ peptides such as Aβ1-40 and Aβ1-42 have been analyzed extensively, the deposition of N-terminally truncated Aβ peptide species has received much less attention, largely because of the lack of specific antibodies.

METHODS

This paper describes the generation and characterization of novel antibodies selective for Aβ4-x peptides and provides immunohistochemical evidence of Aβ4-x in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models.

RESULTS

The Aβ4-x staining pattern was restricted mainly to amyloid plaque cores and cerebral amyloid angiopathy in AD and Down syndrome cases and in both AD mouse models. In contrast, diffuse amyloid deposits were largely negative for Aβ4-x immunoreactivity. No overt intraneuronal staining was observed.

CONCLUSIONS

The findings of this study are consistent with previous reports demonstrating a high aggregation propensity of Aβ4-x peptides and suggest an important role of these N-truncated Aβ species in the process of amyloidogenesis and plaque core formation.

Authors+Show Affiliations

Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany. owirths@gwdg.de. Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany. owirths@gwdg.de.Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany.Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany.Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany. Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany.Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany.Department of Pathology, New York University School of Medicine, New York, NY, USA. Departments of Psychiatry, New York University School of Medicine, New York, NY, USA.Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany. German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany. Institute for Research in Biomedicine (iBiMED), Medical Sciences Department, University of Aveiro, Aveiro, Portugal.Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany. Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Strasse 5, 37075, Goettingen, Germany.Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28978359

Citation

Wirths, Oliver, et al. "N-truncated Aβ4-x Peptides in Sporadic Alzheimer's Disease Cases and Transgenic Alzheimer Mouse Models." Alzheimer's Research & Therapy, vol. 9, no. 1, 2017, p. 80.
Wirths O, Walter S, Kraus I, et al. N-truncated Aβ4-x peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models. Alzheimers Res Ther. 2017;9(1):80.
Wirths, O., Walter, S., Kraus, I., Klafki, H. W., Stazi, M., Oberstein, T. J., ... Weggen, S. (2017). N-truncated Aβ4-x peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models. Alzheimer's Research & Therapy, 9(1), p. 80. doi:10.1186/s13195-017-0309-z.
Wirths O, et al. N-truncated Aβ4-x Peptides in Sporadic Alzheimer's Disease Cases and Transgenic Alzheimer Mouse Models. Alzheimers Res Ther. 2017 Oct 4;9(1):80. PubMed PMID: 28978359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-truncated Aβ4-x peptides in sporadic Alzheimer's disease cases and transgenic Alzheimer mouse models. AU - Wirths,Oliver, AU - Walter,Susanne, AU - Kraus,Inga, AU - Klafki,Hans W, AU - Stazi,Martina, AU - Oberstein,Timo J, AU - Ghiso,Jorge, AU - Wiltfang,Jens, AU - Bayer,Thomas A, AU - Weggen,Sascha, Y1 - 2017/10/04/ PY - 2017/06/21/received PY - 2017/09/11/accepted PY - 2017/10/6/entrez PY - 2017/10/6/pubmed PY - 2018/6/21/medline KW - 5XFAD KW - APP/PS1KI KW - Alzheimer’s disease KW - Immunohistochemistry KW - Mouse model KW - N-truncated Amyloid-β KW - Postmortem SP - 80 EP - 80 JF - Alzheimer's research & therapy JO - Alzheimers Res Ther VL - 9 IS - 1 N2 - BACKGROUND: The deposition of neurotoxic amyloid-β (Aβ) peptides in plaques in the brain parenchyma and in cerebral blood vessels is considered to be a key event in Alzheimer's disease (AD) pathogenesis. Although the presence and impact of full-length Aβ peptides such as Aβ1-40 and Aβ1-42 have been analyzed extensively, the deposition of N-terminally truncated Aβ peptide species has received much less attention, largely because of the lack of specific antibodies. METHODS: This paper describes the generation and characterization of novel antibodies selective for Aβ4-x peptides and provides immunohistochemical evidence of Aβ4-x in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models. RESULTS: The Aβ4-x staining pattern was restricted mainly to amyloid plaque cores and cerebral amyloid angiopathy in AD and Down syndrome cases and in both AD mouse models. In contrast, diffuse amyloid deposits were largely negative for Aβ4-x immunoreactivity. No overt intraneuronal staining was observed. CONCLUSIONS: The findings of this study are consistent with previous reports demonstrating a high aggregation propensity of Aβ4-x peptides and suggest an important role of these N-truncated Aβ species in the process of amyloidogenesis and plaque core formation. SN - 1758-9193 UR - https://www.unboundmedicine.com/medline/citation/28978359/N_truncated_Aβ4_x_peptides_in_sporadic_Alzheimer's_disease_cases_and_transgenic_Alzheimer_mouse_models_ L2 - https://alzres.biomedcentral.com/articles/10.1186/s13195-017-0309-z DB - PRIME DP - Unbound Medicine ER -