Advanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer's disease. 2001

A Wong, and H J Lüth, and W Deuther-Conrad, and S Dukic-Stefanovic, and J Gasic-Milenkovic, and T Arendt, and G Münch
Neuroimmunological Cell Biology, IZKF Leipzig, Johannisallee 30a, 04103, Leipzig, Germany.

Advanced glycation endproducts (AGEs), protein-bound oxidation products of sugars, have been shown to be involved in the pathophysiological processes of Alzheimer's disease (AD). AGEs induce the expression of various pro-inflammatory cytokines and the inducible nitric oxide synthase (iNOS) leading to a state of oxidative stress. AGE modification and resulting crosslinking of protein deposits such as amyloid plaques may contribute to the oxidative stress occurring in AD. The aim of this study was to immunohistochemically compare the localization of AGEs and beta-amyloid (Abeta) with iNOS in the temporal cortex (Area 22) of normal and AD brains. In aged normal individuals as well as early stage AD brains (i.e. no pathological findings in isocortical areas), a few astrocytes showed co-localization of AGE and iNOS in the upper neuronal layers, compared with no astrocytes detected in young controls. In late AD brains, there was a much denser accumulation of astrocytes co-localized with AGE and iNOS in the deeper and particularly upper neuronal layers. Also, numerous neurons with diffuse AGE but not iNOS reactivity and some AGE and iNOS-positive microglia were demonstrated, compared with only a few AGE-reactive neurons and no microglia in controls. Finally, astrocytes co-localized with AGE and iNOS as well as AGE and were found surrounding mature but not diffuse amyloid plaques in the AD brain. Our results show that AGE-positive astrocytes and microglia in the AD brain express iNOS and support the evidence of an AGE-induced oxidative stress occurring in the vicinity of the characteristic lesions of AD. Hence activation of microglia and astrocytes by AGEs with subsequent oxidative stress and cytokine release may be an important progression factor in AD.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D013702 Temporal Lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the OCCIPITAL LOBE. Anterior Temporal Lobe,Brodmann Area 20,Brodmann Area 21,Brodmann Area 22,Brodmann Area 37,Brodmann Area 38,Brodmann Area 52,Brodmann's Area 20,Brodmann's Area 21,Brodmann's Area 22,Brodmann's Area 37,Brodmann's Area 38,Brodmann's Area 52,Inferior Temporal Gyrus,Middle Temporal Gyrus,Parainsular Area,Fusiform Gyrus,Gyrus Fusiformis,Gyrus Temporalis Superior,Inferior Horn of Lateral Ventricle,Inferior Horn of the Lateral Ventricle,Lateral Occipito-Temporal Gyrus,Lateral Occipitotemporal Gyrus,Occipitotemporal Gyrus,Planum Polare,Superior Temporal Gyrus,Temporal Cortex,Temporal Gyrus,Temporal Horn,Temporal Horn of the Lateral Ventricle,Temporal Operculum,Temporal Region,Temporal Sulcus,Anterior Temporal Lobes,Area 20, Brodmann,Area 20, Brodmann's,Area 21, Brodmann,Area 21, Brodmann's,Area 22, Brodmann,Area 22, Brodmann's,Area 37, Brodmann,Area 37, Brodmann's,Area 38, Brodmann,Area 38, Brodmann's,Area 52, Brodmann,Area 52, Brodmann's,Area, Parainsular,Areas, Parainsular,Brodmanns Area 20,Brodmanns Area 21,Brodmanns Area 22,Brodmanns Area 37,Brodmanns Area 38,Brodmanns Area 52,Cortex, Temporal,Gyrus, Fusiform,Gyrus, Inferior Temporal,Gyrus, Lateral Occipito-Temporal,Gyrus, Lateral Occipitotemporal,Gyrus, Middle Temporal,Gyrus, Occipitotemporal,Gyrus, Superior Temporal,Gyrus, Temporal,Horn, Temporal,Lateral Occipito Temporal Gyrus,Lobe, Anterior Temporal,Lobe, Temporal,Occipito-Temporal Gyrus, Lateral,Occipitotemporal Gyrus, Lateral,Operculum, Temporal,Parainsular Areas,Region, Temporal,Sulcus, Temporal,Temporal Cortices,Temporal Gyrus, Inferior,Temporal Gyrus, Middle,Temporal Gyrus, Superior,Temporal Horns,Temporal Lobe, Anterior,Temporal Lobes,Temporal Lobes, Anterior,Temporal Regions
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D016610 Tissue Embedding The technique of placing cells or tissue in a supporting medium so that thin sections can be cut using a microtome. The medium can be paraffin wax (PARAFFIN EMBEDDING) or plastics (PLASTIC EMBEDDING) such as epoxy resins. Embedding, Tissue

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