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Deposition of C-terminally truncated Aβ species Aβ37 and Aβ39 in Alzheimer's disease and transgenic mouse models.
Acta Neuropathol Commun. 2016 Mar 08; 4:24.AN

Abstract

In Alzheimer's disease (AD) a variety of amyloid β-peptides (Aβ) are deposited in the form of extracellular diffuse and neuritic plaques (NP), as well as within the vasculature. The generation of Aβ from its precursor, the amyloid precursor protein (APP), is a highly complex procedure that involves subsequent proteolysis of APP by β- and γ-secretases. Brain accumulation of Aβ due to impaired Aβ degradation and/or altered ratios between the different Aβ species produced is believed to play a pivotal role in AD pathogenesis. While the presence of Aβ40 and Aβ42 in vascular and parenchymal amyloid have been subject of extensive studies, the deposition of carboxyterminal truncated Aβ peptides in AD has not received comparable attention. In the current study, we for the first time demonstrate the immunohistochemical localization of Aβ37 and Aβ39 in human sporadic AD (SAD). Our study further included the analysis of familial AD (FAD) cases carrying the APP mutations KM670/671NL, E693G and I716F, as well as a case of the PSEN1 ΔExon9 mutation. Aβ37 and Aβ39 were found to be widely distributed within the vasculature in the brains of the majority of studied SAD and FAD cases, the latter also presenting considerable amounts of Aβ37 containing NPs. In addition, both peptides were found to be present in extracellular plaques but only scarce within the vasculature in brains of a variety of transgenic AD mouse models. Taken together, our study indicates the importance of C-terminally truncated Aβ in sporadic and familial AD and raises questions about how these species are generated and regulated.

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Authors+Show Affiliations

Reinert J
Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
Richard BC
Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
Klafki HW
Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Str. 5, 37075, Göttingen, Germany.
Friedrich B
Synaptic Systems, Göttingen, Germany.
Bayer TA
Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, Göttingen, Germany. Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Str. 5, 37075, Göttingen, Germany.
Wiltfang J
Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Str. 5, 37075, Göttingen, Germany.
Kovacs GG
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Ingelsson M
Department of Public Health and Caring Sciences, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden.
Lannfelt L
Department of Public Health and Caring Sciences, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden.
Paetau A
Department of Pathology, University and University Hospital of Helsinki, Helsinki, Finland.
Bergquist J
Analytical Chemistry, Department of Chemistry - Biomedical Centre and SciLifeLab, Uppsala University, Uppsala, Sweden.
Wirths O
Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, Göttingen, Germany. owirths@gwdg.de. Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Str. 5, 37075, Göttingen, Germany. owirths@gwdg.de.

MeSH

Age FactorsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainDisease Models, AnimalDown SyndromeFemaleGene Expression RegulationHumansMaleMiceMice, Inbred C57BLMice, TransgenicMiddle AgedMutationPeptide FragmentsPresenilin-1

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26955942

Citation

Reinert, Jochim, et al. "Deposition of C-terminally Truncated Aβ Species Aβ37 and Aβ39 in Alzheimer's Disease and Transgenic Mouse Models." Acta Neuropathologica Communications, vol. 4, 2016, p. 24.
Reinert J, Richard BC, Klafki HW, et al. Deposition of C-terminally truncated Aβ species Aβ37 and Aβ39 in Alzheimer's disease and transgenic mouse models. Acta Neuropathol Commun. 2016;4:24.
Reinert, J., Richard, B. C., Klafki, H. W., Friedrich, B., Bayer, T. A., Wiltfang, J., Kovacs, G. G., Ingelsson, M., Lannfelt, L., Paetau, A., Bergquist, J., & Wirths, O. (2016). Deposition of C-terminally truncated Aβ species Aβ37 and Aβ39 in Alzheimer's disease and transgenic mouse models. Acta Neuropathologica Communications, 4, 24. https://doi.org/10.1186/s40478-016-0294-7
Reinert J, et al. Deposition of C-terminally Truncated Aβ Species Aβ37 and Aβ39 in Alzheimer's Disease and Transgenic Mouse Models. Acta Neuropathol Commun. 2016 Mar 8;4:24. PubMed PMID: 26955942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deposition of C-terminally truncated Aβ species Aβ37 and Aβ39 in Alzheimer's disease and transgenic mouse models. AU - Reinert,Jochim, AU - Richard,Bernhard C, AU - Klafki,Hans W, AU - Friedrich,Beate, AU - Bayer,Thomas A, AU - Wiltfang,Jens, AU - Kovacs,Gabor G, AU - Ingelsson,Martin, AU - Lannfelt,Lars, AU - Paetau,Anders, AU - Bergquist,Jonas, AU - Wirths,Oliver, Y1 - 2016/03/08/ PY - 2016/02/10/received PY - 2016/02/26/accepted PY - 2016/3/10/entrez PY - 2016/3/10/pubmed PY - 2016/10/16/medline SP - 24 EP - 24 JF - Acta neuropathologica communications JO - Acta Neuropathol Commun VL - 4 N2 - In Alzheimer's disease (AD) a variety of amyloid β-peptides (Aβ) are deposited in the form of extracellular diffuse and neuritic plaques (NP), as well as within the vasculature. The generation of Aβ from its precursor, the amyloid precursor protein (APP), is a highly complex procedure that involves subsequent proteolysis of APP by β- and γ-secretases. Brain accumulation of Aβ due to impaired Aβ degradation and/or altered ratios between the different Aβ species produced is believed to play a pivotal role in AD pathogenesis. While the presence of Aβ40 and Aβ42 in vascular and parenchymal amyloid have been subject of extensive studies, the deposition of carboxyterminal truncated Aβ peptides in AD has not received comparable attention. In the current study, we for the first time demonstrate the immunohistochemical localization of Aβ37 and Aβ39 in human sporadic AD (SAD). Our study further included the analysis of familial AD (FAD) cases carrying the APP mutations KM670/671NL, E693G and I716F, as well as a case of the PSEN1 ΔExon9 mutation. Aβ37 and Aβ39 were found to be widely distributed within the vasculature in the brains of the majority of studied SAD and FAD cases, the latter also presenting considerable amounts of Aβ37 containing NPs. In addition, both peptides were found to be present in extracellular plaques but only scarce within the vasculature in brains of a variety of transgenic AD mouse models. Taken together, our study indicates the importance of C-terminally truncated Aβ in sporadic and familial AD and raises questions about how these species are generated and regulated. SN - 2051-5960 UR - https://www.unboundmedicine.com/medline/citation/26955942/Deposition_of_C_terminally_truncated_Aβ_species_Aβ37_and_Aβ39_in_Alzheimer's_disease_and_transgenic_mouse_models_ DB - PRIME DP - Unbound Medicine ER -