Advanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer’s disease

Wong, Amanda; Lüth, Hans-Joachim; Deuther‐Conrad, Winnie; Dukić-Stefanović, Sladjana; Gasic-Milenkovic, Jovana; Arendt, Thomas; Münch, Gerald

doi:10.1016/s0006-8993(01)02872-4

Cited by 145 publications

(98 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As there is evidence for co‐localization of AGEs in AD neurotic plaques (Wong et al ., 2001), we further investigated the involvement of AGEs due to irradiation diet in Aβ aggregation. Levels of AGEs in brain tissue were measured by dot blot.…”

Section: Resultsmentioning

confidence: 99%

“…The learning curve of WT mice was not affected by H‐AGE diet as reflected in similar memory and learning performances in the acquisition phase to those of WT mice on R‐AGE diet. This suggests higher vulnerability of brains susceptible to AD neuropathology to high dietary AGEs levels consistent with findings of co‐localization of AGEs with neuritic plaques in human AD brains (Wong et al ., 2001; Cai et al ., 2014). …”

Section: Discussionmentioning

confidence: 99%

“…In addition, levels of AGEs were significantly higher (~twofold) in hippocampal insoluble Aβ fraction in the Tg2576 group on H‐AGE diet compared to the other three groups as shown in Fig. 5, suggesting that exogenous AGEs pass the BBB and may potentiate Aβ aggregation in line with evidence of AGE surrounding mature amyloid plaques in the AD brains (Wong et al ., 2001). …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

et al. 2016

View full text Add to dashboard Cite

SummaryThere is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42, AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD‐like model mice on high‐AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood–brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle‐linked disease epidemic.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These explanations make it logical to suggest that microglia are associated with lysed cell bodies (dense-core plaques) where lysosomal enzymes, cellular DNA and other factors such as advanced glycation endproducts [68] known to be sufficient to induce microglial activation are released from injured or dying neurons and become accessible to cause the microglial activation. In support, in vitro activation of microglia by A␤ aggregate in the absence of co-factors is typically weak [41] as the material in the diffuse plaques, perhaps only amyloid, lack these important and potent microglial-activating materials.…”

Section: Unique Mechanisms Of Plaque Formationmentioning

confidence: 99%

The microglial phagocytic role with specific plaque types in the Alzheimer disease brain

D’Andrea

Cole

Ard

2004

Neurobiology of Aging

193

131

View full text Add to dashboard Cite

Alzheimer disease (AD) involves glial inflammation associated with amyloid plaques. The role of the microglial cells in the AD brain is controversial, as it remains unclear if the microglia form the amyloid fibrils of plaques or react to them in a macrophage-phagocytic role. Also, it is not known why microglia are preferentially associated with some amyloid plaque types. This review will provide substantial evidence to support the phagocytic role of microglia in the brain as well as explain why microglia are generally associated with specific plaque types that may be explained through their unique mechanisms of formation. In summary, the data presented suggests that plaque associated microglial activation is typically subsequent to specific amyloid plaque formations in the AD brain.

show abstract

“…Several markers of oxidative stress are increased in brain tissue from Alzheimer's patients, including advanced glycation end products (AGEs; Vitek et al 1994;Yan et al 1994), o,o¢-dityrosine (Hensley et al 1998), lipid oxidation products Pratico et al 1998), protein carbonyls (Smith et al 1998), oxidized DNA (Mecocci et al 1994;Gabbita et al 1998), and 3-nitrotyrosine . Oxidative damage occurs early in the neurodegenerative process (Nunomura et al 2001) and co-localization of oxidative stress markers with both neurofibrillary tangles (Good et al 1996;Sayre et al 1997;Smith et al 1997) and amyloid plaques (Smith et al 1994;Vitek et al 1994;Wong et al 2001;McLellan et al 2003) supports a role of oxidants in disease progression. Generation of reactive intermediates in AD brain has been attributed to b-amyloid peptide itself (Butterfield et al 2001), dysfunctional mitochondria (Beal 1996), or increased concentrations of redox-active metal ions (Bush 2003).…”

mentioning

confidence: 97%

Neuronal expression of myeloperoxidase is increased in Alzheimer's disease

Green

Mendez

Jacob

et al. 2004

Journal of Neurochemistry

280

196

View full text Add to dashboard Cite

Myeloperoxidase, a heme protein expressed by professional phagocytic cells, generates an array of oxidants which are proposed to contribute to tissue damage during inflammation. We now report that enzymatically active myeloperoxidase and its characteristic amino acid oxidation products are present in human brain. Further, expression of myeloperoxidase is increased in brain tissue showing Alzheimer's neuropathology. Consistent with expression in phagocytic cells, myeloperoxidase immunoreactivity was present in some activated microglia in Alzheimer brains. However, the majority of immunoreactive material in brain localized with amyloid plaques and, surprisingly, neurons including granule and pyramidal neurons of the hippocampus. Confirming neuronal localization of the enzyme, several neuronal cell lines as well as primary neuronal cultures expressed myeloperoxidase protein. Myeloperoxidase mRNA was also detected in neuronal cell lines. These results reveal the unexpected presence of myeloperoxidase in neurons. The increase in neuronal myeloperoxidase expression we observed in Alzheimer disease brains raises the possibility that the enzyme contributes to the oxidative stress implicated in the pathogenesis of the neurodegenerative disorder.

show abstract

Advanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer’s disease

Cited by 145 publications

References 50 publications

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

The microglial phagocytic role with specific plaque types in the Alzheimer disease brain

Neuronal expression of myeloperoxidase is increased in Alzheimer's disease

Contact Info

Product

Resources

About