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

Plagg B, Marksteiner J, Kniewallner KM, Humpel C - Biogerontology (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Flow cytometry (FACS) analysis in mouse (a, c, e, g) and human (b, d, f, h) platelets shows a common population of cells in forward and sideward scatter (a, b) and markedly expressed CD62P in mouse (c, green) but less in human (d, green) platelets, compared to an IgG control (red). Apoptosis was assessed using Annexin IV staining (e, f), showing examples of no apoptosis in mice (e) or increased apoptosis in humans (f, arrow). Necrosis was measured using 7-amino actinomycin D (7-AAD) in a mouse example (g) or co-expressed in apoptotic human platelets (h). (Color figure online)
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Fig1: Flow cytometry (FACS) analysis in mouse (a, c, e, g) and human (b, d, f, h) platelets shows a common population of cells in forward and sideward scatter (a, b) and markedly expressed CD62P in mouse (c, green) but less in human (d, green) platelets, compared to an IgG control (red). Apoptosis was assessed using Annexin IV staining (e, f), showing examples of no apoptosis in mice (e) or increased apoptosis in humans (f, arrow). Necrosis was measured using 7-amino actinomycin D (7-AAD) in a mouse example (g) or co-expressed in apoptotic human platelets (h). (Color figure online)

Mentions: Mouse platelets from wildtype mice (C57BL/6N) were isolated and characterized using FACS analysis, displaying a common population and marked CD62P expression (Fig. 1). Apoptotic and necrotic cell death was very low in young animals (<0.5 %) and slightly increased in older mice (<9 %). Serotonin levels were around 60 ng/mg protein and increased in older animals (Tables 1, 2, 3). APP like immunoreactivity was detectable in Western Blot as a single band at approximately 110 kDa (Fig. 2), but did not markedly change during aging. APP as measured by ELISA was found to be approximately 2 ng/mg protein which increased in older animals (Table 3). The release of sAPPβ was approximately 3 ng/ml × 12.5 µg × 150 min in WT mice.Fig. 1


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

Plagg B, Marksteiner J, Kniewallner KM, Humpel C - Biogerontology (2015)

Flow cytometry (FACS) analysis in mouse (a, c, e, g) and human (b, d, f, h) platelets shows a common population of cells in forward and sideward scatter (a, b) and markedly expressed CD62P in mouse (c, green) but less in human (d, green) platelets, compared to an IgG control (red). Apoptosis was assessed using Annexin IV staining (e, f), showing examples of no apoptosis in mice (e) or increased apoptosis in humans (f, arrow). Necrosis was measured using 7-amino actinomycin D (7-AAD) in a mouse example (g) or co-expressed in apoptotic human platelets (h). (Color figure online)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4487346&req=5

Fig1: Flow cytometry (FACS) analysis in mouse (a, c, e, g) and human (b, d, f, h) platelets shows a common population of cells in forward and sideward scatter (a, b) and markedly expressed CD62P in mouse (c, green) but less in human (d, green) platelets, compared to an IgG control (red). Apoptosis was assessed using Annexin IV staining (e, f), showing examples of no apoptosis in mice (e) or increased apoptosis in humans (f, arrow). Necrosis was measured using 7-amino actinomycin D (7-AAD) in a mouse example (g) or co-expressed in apoptotic human platelets (h). (Color figure online)
Mentions: Mouse platelets from wildtype mice (C57BL/6N) were isolated and characterized using FACS analysis, displaying a common population and marked CD62P expression (Fig. 1). Apoptotic and necrotic cell death was very low in young animals (<0.5 %) and slightly increased in older mice (<9 %). Serotonin levels were around 60 ng/mg protein and increased in older animals (Tables 1, 2, 3). APP like immunoreactivity was detectable in Western Blot as a single band at approximately 110 kDa (Fig. 2), but did not markedly change during aging. APP as measured by ELISA was found to be approximately 2 ng/mg protein which increased in older animals (Table 3). The release of sAPPβ was approximately 3 ng/ml × 12.5 µg × 150 min in WT mice.Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus