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Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease

Alzheimer’s disease (AD) is a severe neurodegenerative disorder characterized mainly by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss. Blood platelets contain the neurotransmitter serotonin and amyloid-precursor protein (APP), and may thus be useful as a p...

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Autores principales: Plagg, Barbara, Marksteiner, Josef, Kniewallner, Kathrin M., Humpel, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487346/
https://www.ncbi.nlm.nih.gov/pubmed/25947203
http://dx.doi.org/10.1007/s10522-015-9580-1
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author Plagg, Barbara
Marksteiner, Josef
Kniewallner, Kathrin M.
Humpel, Christian
author_facet Plagg, Barbara
Marksteiner, Josef
Kniewallner, Kathrin M.
Humpel, Christian
author_sort Plagg, Barbara
collection PubMed
description Alzheimer’s disease (AD) is a severe neurodegenerative disorder characterized mainly by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss. Blood platelets contain the neurotransmitter serotonin and amyloid-precursor protein (APP), and may thus be useful as a peripheral biomarker for AD. The aim of the present study was to functionally characterize platelets by FACS, to examine alterations in APP expression and secretion, and to measure serotonin levels in hypercholesterolemia mice with AD-like pathology and in two AD mouse models, the triple transgenic AD model (3xTg) and the APP overexpressing AD model with the Swedish–Dutch–Iowa mutations (APP_SweDI). These data are supplemented with epidermal growth factor (EGF) levels and compared with changes observed in platelets of patients with AD. We observed decreased platelet APP isoforms in 3xTg mice and patients with AD when analysed by means of Western blot. In patients, a significant increase of APP levels was observed when assessed by ELISA. Secreted APPβ proved to be altered amongst all three animal models of AD at different time points and in human patients with AD. Serotonin levels were only reduced in 7 and 14 month old 3xTg mice. Moreover, we found significantly lower EGF levels in human AD patients and could thereby reproduce previous findings. Taken together, our data confirm that platelets are dysfunctional in AD, however, results from AD animal models do not coincide in all aspects, and markedly differ when compared to AD patients. We support previous data that APP, as well as EGF, could become putative biomarkers for diagnosing AD in human platelets.
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spelling pubmed-44873462015-07-07 Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease Plagg, Barbara Marksteiner, Josef Kniewallner, Kathrin M. Humpel, Christian Biogerontology Research Article Alzheimer’s disease (AD) is a severe neurodegenerative disorder characterized mainly by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss. Blood platelets contain the neurotransmitter serotonin and amyloid-precursor protein (APP), and may thus be useful as a peripheral biomarker for AD. The aim of the present study was to functionally characterize platelets by FACS, to examine alterations in APP expression and secretion, and to measure serotonin levels in hypercholesterolemia mice with AD-like pathology and in two AD mouse models, the triple transgenic AD model (3xTg) and the APP overexpressing AD model with the Swedish–Dutch–Iowa mutations (APP_SweDI). These data are supplemented with epidermal growth factor (EGF) levels and compared with changes observed in platelets of patients with AD. We observed decreased platelet APP isoforms in 3xTg mice and patients with AD when analysed by means of Western blot. In patients, a significant increase of APP levels was observed when assessed by ELISA. Secreted APPβ proved to be altered amongst all three animal models of AD at different time points and in human patients with AD. Serotonin levels were only reduced in 7 and 14 month old 3xTg mice. Moreover, we found significantly lower EGF levels in human AD patients and could thereby reproduce previous findings. Taken together, our data confirm that platelets are dysfunctional in AD, however, results from AD animal models do not coincide in all aspects, and markedly differ when compared to AD patients. We support previous data that APP, as well as EGF, could become putative biomarkers for diagnosing AD in human platelets. Springer Netherlands 2015-05-07 2015 /pmc/articles/PMC4487346/ /pubmed/25947203 http://dx.doi.org/10.1007/s10522-015-9580-1 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research Article
Plagg, Barbara
Marksteiner, Josef
Kniewallner, Kathrin M.
Humpel, Christian
Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease
title Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease
title_full Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease
title_fullStr Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease
title_full_unstemmed Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease
title_short Platelet dysfunction in hypercholesterolemia mice, two Alzheimer’s disease mouse models and in human patients with Alzheimer’s disease
title_sort platelet dysfunction in hypercholesterolemia mice, two alzheimer’s disease mouse models and in human patients with alzheimer’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487346/
https://www.ncbi.nlm.nih.gov/pubmed/25947203
http://dx.doi.org/10.1007/s10522-015-9580-1
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