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Deposition of C-ter...
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, Jochim (author)
- Univ Gottingen, Univ Med Ctr UMG, Div Mol Psychiat, D-37075 Gottingen, Germany.
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- Richard, Bernhard C. (author)
- Univ Gottingen, Univ Med Ctr UMG, Div Mol Psychiat, D-37075 Gottingen, Germany.
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- Klafki, Hans W. (author)
- Univ Gottingen, Univ Med Ctr UMG, Dept Psychiat & Psychotherapy, Von Siebold Str 5, D-37075 Gottingen, Germany.
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- Friedrich, Beate (author)
- Synapt Syst, Gottingen, Germany.
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- Bayer, Thomas A. (author)
- Univ Gottingen, Univ Med Ctr UMG, Div Mol Psychiat, D-37075 Gottingen, Germany.;Univ Gottingen, Univ Med Ctr UMG, Dept Psychiat & Psychotherapy, Von Siebold Str 5, D-37075 Gottingen, Germany.
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- Wiltfang, Jens (author)
- Univ Gottingen, Univ Med Ctr UMG, Dept Psychiat & Psychotherapy, Von Siebold Str 5, D-37075 Gottingen, Germany.
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- Kovacs, Gabor G. (author)
- Med Univ Vienna, Inst Neurol, Vienna, Austria.
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik
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- Lannfelt, Lars (author)
- Uppsala universitet,Geriatrik
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- Paetau, Anders (author)
- Univ Helsinki, Dept Pathol, Helsinki, Finland.;Univ Helsinki Hosp, Helsinki, Finland.
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- Bergquist, Jonas (author)
- Uppsala universitet,Analytisk kemi,Science for Life Laboratory, SciLifeLab
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- Wirths, Oliver (author)
- Univ Gottingen, Univ Med Ctr UMG, Div Mol Psychiat, D-37075 Gottingen, Germany.;Univ Gottingen, Univ Med Ctr UMG, Dept Psychiat & Psychotherapy, Von Siebold Str 5, D-37075 Gottingen, Germany.
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Univ Gottingen, Univ Med Ctr UMG, Div Mol Psychiat, D-37075 Gottingen, Germany Univ Gottingen, Univ Med Ctr UMG, Dept Psychiat & Psychotherapy, Von Siebold Str 5, D-37075 Gottingen, Germany. (creator_code:org_t)
- 2016-03-08
- 2016
- English.
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In: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 4
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Abstract
Subject headings
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- 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 headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Alzheimer
- C-terminal truncation
- Amyloid precursor protein
- Transgenic mice
- A beta 37
- A beta 39
- Immunohistochemistry
- Mass spectrometry
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Reinert, Jochim
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Richard, Bernhar ...
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Klafki, Hans W.
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Friedrich, Beate
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Bayer, Thomas A.
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Wiltfang, Jens
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show more...
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Kovacs, Gabor G.
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Ingelsson, Marti ...
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Lannfelt, Lars
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Paetau, Anders
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Bergquist, Jonas
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Wirths, Oliver
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Acta neuropathol ...
- By the university
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Uppsala University