Glycation and microglial reaction in lesions of Alzheimer's disease

Dickson, Dennis W.; Sinicropi, S.; Yen, Shu Hui; Ko, Li Wen; Mattiace, Linda A.; Bucala, Richard; Vlassara, Helen

doi:10.1016/0197-4580(96)00116-9

Cited by 73 publications

(33 citation statements)

References 48 publications

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“…For instance, the Honolulu Asia Aging Study found that having both T2D and the APOE ε4 allele led to an increased risk in the number of hippocampal neuritic plaques, hippocampal and cortical NFTs, and the risk of cerebral amyloid angiopathy. Consistent with that, co-localization of APOE and AGEs—which in addition to their atherogenic effect—have been found in amyloid deposits and NFTs (Dickson et al, 1996), and both co-localization and interaction between APOE ε4 and AGEs have been linked to plaques deposition and NFTs (Y. M. Li, 1997; Sasaki, 1998).…”

Section: T2d Involvement In Ad Neuropathologysupporting

confidence: 66%

Neuropathology of type 2 diabetes: a short review on insulin-related mechanisms

Guerrero‐Berroa

Schmeidler

Beeri

2014

European Neuropsychopharmacology

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Postmortem studies have shown that cerebrovascular disease (CVD) neuropathology occurs frequently in type 2 diabetes (T2D) through mechanisms associated with chronic hyperglycemia such as advanced glycation end-products (AGEs). The involvement of T2D in Alzheimer's disease (AD)-type neuropathology has been more controversial. While postmortem data from animal studies have supported the involvement of T2D in AD-type neuropathology through insulin mechanism that may affect the development of neuritic plaques and neurofibrillary tangles (NFTs), findings from postmortem studies in humans, of the association of T2D with AD, have been mainly negative. To complicate matters, medications to treat T2D have been implicated in reduced AD-type neuropathology. In this review we summarize the literature on animal and human postmortem studies of T2D neuropathology, mainly the mechanisms involved in hyperglycemia-related CVD neuropathology and hyperinsulinemia-related AD-type neuropathology.

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Section: T2d Involvement In Ad Neuropathologysupporting

confidence: 66%

Neuropathology of type 2 diabetes: a short review on insulin-related mechanisms

Guerrero‐Berroa

Schmeidler

Beeri

2014

European Neuropsychopharmacology

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“…In addition, this relationship did not differ by sex, APOE4 genotype, BMI, or diabetes status suggesting its generality. MG derivatives are common reactive AGE intermediates found elevated in older subjects, and together with terminal AGEs, such as carboxy-methyllysine (CML) correlate with increased levels of oxidative stress(17) and markers of inflammation(10), processes which are inherently associated with AD neuropathology(2, 23, 24). Elevated AGEs are also associated with diabetes(1) and vascular disease(25), conditions also associated with AD(3, 26).…”

Section: Discussionmentioning

confidence: 99%

Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals

Beeri

Moshier

Schmeidler

et al. 2011

Mechanisms of Ageing and Development

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125

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Background Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. Methods Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an APOE4 allele), and kidney function. sMG was assessed by ELISA. Results The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p=0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and APOE4 genotype were not significant. Conclusions Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, APOE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise.

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“…AGE accumulation is found in senile plaques and neurofibrillary tangles of persons with AD [175][176][177]. In the cerebrospinal fluid of patients with AD increased levels of Amadori products on all the major proteins are found.…”

Section: Alzheimer's Disease (Ad)mentioning

confidence: 99%

The Clinical Relevance of Advanced Glycation Endproducts (AGE) and Recent Developments in Pharmaceutics to Reduce AGE Accumulation

Smit¹,

Lutgers

2004

CMC

116

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Advanced glycation endproducts (AGE) are a class of compounds resulting from glycation and oxidation of proteins, lipids or nucleic acids. Glycation is the non-enzymatic addition or insertion of saccharide derivatives to these molecules. This leads to the formation of intermediary Schiff bases and Amadori products and finally to irreversible AGE. This classical view has been modified in recent years with recognition of the importance of oxidative and carbonyl stress in endogenous AGE formation. AGE may also have exogenous sources, in certain foods and tobacco smoke. A whole class of specific and non-specific receptors binding AGE has been characterized. Apart from cross-linking of proteins by AGE, the effects of receptor stimulation contribute to the development of chronic complications of conditions like diabetes mellitus, renal failure, and atherosclerosis. Possible interventions to reduce the effects of AGE accumulation include AGE formation inhibitors or breakers, or receptor blockers, but possibly also dietary interventions. Some of the problems with current assay or diagnostic techniques, and several unresolved issues on the role of AGE in disease will be discussed. Our review will focus on the clinical and pharmaceutical implications of these developments.

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Glycation and microglial reaction in lesions of Alzheimer's disease

Cited by 73 publications

References 48 publications

Neuropathology of type 2 diabetes: a short review on insulin-related mechanisms

Neuropathology of type 2 diabetes: a short review on insulin-related mechanisms

Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals

The Clinical Relevance of Advanced Glycation Endproducts (AGE) and Recent Developments in Pharmaceutics to Reduce AGE Accumulation

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