Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus
It has been extensively reported that diabetes mellitus (DM) patients have a higher risk of developing Alzheimer's disease (AD), but a mechanistic connection between both pathologies has not been provided so far. Carbohydrate-derived advanced glycation endproducts (AGEs) have been implicated in...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-01-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109002496 |
| _version_ | 1819119810801303552 |
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| author | Tony Valente Alejandro Gella Xavier Fernàndez-Busquets Mercedes Unzeta Nuria Durany |
| author_facet | Tony Valente Alejandro Gella Xavier Fernàndez-Busquets Mercedes Unzeta Nuria Durany |
| author_sort | Tony Valente |
| collection | DOAJ |
| description | It has been extensively reported that diabetes mellitus (DM) patients have a higher risk of developing Alzheimer's disease (AD), but a mechanistic connection between both pathologies has not been provided so far. Carbohydrate-derived advanced glycation endproducts (AGEs) have been implicated in the chronic complications of DM and have been reported to play an important role in the pathogenesis of AD. The earliest histopathological manifestation of AD is the apparition of extracellular aggregates of the amyloid β peptide (Aβ). To investigate possible correlations between AGEs and Aβ aggregates with both pathologies, we have performed an immuhistochemical study in human post-mortem samples of AD, AD with diabetes (ADD), diabetic and nondemented controls. ADD brains showed increased number of Aβ dense plaques and receptor for AGEs (RAGE)-positive and Tau-positive cells, higher AGEs levels and major microglial activation, compared to AD brain. Our results indicate that ADD patients present a significant increase of cell damage through a RAGE-dependent mechanism, suggesting that AGEs may promote the generation of an oxidative stress vicious cycle, which can explain the severe progression of patients with both pathologies. |
| first_indexed | 2024-12-22T06:10:42Z |
| format | Article |
| id | doaj.art-ed5dbc6172514d10b0c13b854e16f713 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T06:10:42Z |
| publishDate | 2010-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ed5dbc6172514d10b0c13b854e16f7132022-12-21T18:36:15ZengElsevierNeurobiology of Disease1095-953X2010-01-013716776Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitusTony Valente0Alejandro Gella1Xavier Fernàndez-Busquets2Mercedes Unzeta3Nuria Durany4Department of Biochemistry and Molecular Biology, School of Medicine, Neuroscience Institute, Autonomous University of Barcelona, Bellaterra-08193, Barcelona, SpainFaculty of Medicine and Health Sciences, International University of Catalonia, Josep Trueta s/n, Sant Cugat del Vallès-08195, SpainNanobioengineering Group, Institute for Bioengineering of Catalonia, and Biomolecular Interactions Team, Nanoscience and Nanotechnology Institute, Barcelona Science Park, University of Barcelona, Josep Samitier1-5, Barcelona-08028, SpainDepartment of Biochemistry and Molecular Biology, School of Medicine, Neuroscience Institute, Autonomous University of Barcelona, Bellaterra-08193, Barcelona, SpainFaculty of Medicine and Health Sciences, International University of Catalonia, Josep Trueta s/n, Sant Cugat del Vallès-08195, Spain; Corresponding author. Fax: + 34 93 5042001.It has been extensively reported that diabetes mellitus (DM) patients have a higher risk of developing Alzheimer's disease (AD), but a mechanistic connection between both pathologies has not been provided so far. Carbohydrate-derived advanced glycation endproducts (AGEs) have been implicated in the chronic complications of DM and have been reported to play an important role in the pathogenesis of AD. The earliest histopathological manifestation of AD is the apparition of extracellular aggregates of the amyloid β peptide (Aβ). To investigate possible correlations between AGEs and Aβ aggregates with both pathologies, we have performed an immuhistochemical study in human post-mortem samples of AD, AD with diabetes (ADD), diabetic and nondemented controls. ADD brains showed increased number of Aβ dense plaques and receptor for AGEs (RAGE)-positive and Tau-positive cells, higher AGEs levels and major microglial activation, compared to AD brain. Our results indicate that ADD patients present a significant increase of cell damage through a RAGE-dependent mechanism, suggesting that AGEs may promote the generation of an oxidative stress vicious cycle, which can explain the severe progression of patients with both pathologies.http://www.sciencedirect.com/science/article/pii/S0969996109002496AbetaAlzheimer's diseaseRAGEAGEsDiabetesImmunohistochemistry |
| spellingShingle | Tony Valente Alejandro Gella Xavier Fernàndez-Busquets Mercedes Unzeta Nuria Durany Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus Neurobiology of Disease Abeta Alzheimer's disease RAGE AGEs Diabetes Immunohistochemistry |
| title | Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus |
| title_full | Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus |
| title_fullStr | Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus |
| title_full_unstemmed | Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus |
| title_short | Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus |
| title_sort | immunohistochemical analysis of human brain suggests pathological synergism of alzheimer s disease and diabetes mellitus |
| topic | Abeta Alzheimer's disease RAGE AGEs Diabetes Immunohistochemistry |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109002496 |
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