Deposition of C-terminally truncated A beta species A beta 37 and A beta 39 in Alzheimer's disease and transgenic mouse models

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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 A beta species A beta 37 and A beta 39 in Alzheimer's disease and transgenic mouse models ' , Acta Neuropathologica Communications , vol. 4 , 24 . https://doi.org/10.1186/s40478-016-0294-7

Title: Deposition of C-terminally truncated A beta species A beta 37 and A beta 39 in Alzheimer's disease and transgenic mouse models
Author: Reinert, Jochim; Richard, Bernhard C.; Klafki, Hans W.; Friedrich, Beate; Bayer, Thomas A.; Wiltfang, Jens; Kovacs, Gabor G.; Ingelsson, Martin; Lannfelt, Lars; Paetau, Anders; Bergquist, Jonas; Wirths, Oliver
Contributor organization: Medicum
Department of Pathology
Clinicum
University of Helsinki
Date: 2016-03-08
Language: eng
Number of pages: 12
Belongs to series: Acta Neuropathologica Communications
ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-016-0294-7
URI: http://hdl.handle.net/10138/233175
Abstract: 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.
Subject: Alzheimer
C-terminal truncation
Amyloid precursor protein
Transgenic mice
A beta 37
A beta 39
Immunohistochemistry
Mass spectrometry
AMYLOID PRECURSOR PROTEIN
GAMMA-SECRETASE ACTIVITY
PLAQUE CORE
CEREBROSPINAL-FLUID
PEPTIDES
MUTATIONS
APP
GENERATION
A-BETA(42)
MICE
3112 Neurosciences
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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