Deposition of C-terminally truncated A beta species A beta 37 and A beta 39 in Alzheimer's disease and transgenic mouse models
2016 (English)In: Acta neuropathologica communications, ISSN 1509-409X, E-ISSN 2051-5960, Vol. 4, 24Article in journal (Refereed) PublishedText
In Alzheimer's disease (AD) a variety of amyloid beta-peptides (A beta) are deposited in the form of extracellular diffuse and neuritic plaques (NP), as well as within the vasculature. The generation of A beta from its precursor, the amyloid precursor protein (APP), is a highly complex procedure that involves subsequent proteolysis of APP by beta-and gamma-secretases. Brain accumulation of A beta due to impaired A beta degradation and/or altered ratios between the different A beta species produced is believed to play a pivotal role in AD pathogenesis. While the presence of A beta 40 and A beta 42 in vascular and parenchymal amyloid have been subject of extensive studies, the deposition of carboxyterminal truncated A beta peptides in AD has not received comparable attention. In the current study, we for the first time demonstrate the immunohistochemical localization of A beta 37 and A beta 39 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 Delta Exon9 mutation. A beta 37 and A beta 39 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 A beta 37 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 A beta in sporadic and familial AD and raises questions about how these species are generated and regulated.
Place, publisher, year, edition, pages
2016. Vol. 4, 24
Alzheimer, C-terminal truncation, Amyloid precursor protein, Transgenic mice, A beta 37, A beta 39, Immunohistochemistry, Mass spectrometry
IdentifiersURN: urn:nbn:se:uu:diva-282802DOI: 10.1186/s40478-016-0294-7ISI: 000371589300001PubMedID: 26955942OAI: oai:DiVA.org:uu-282802DiVA: diva2:919163