Type II Diabetes Mellitus Accelerates Age-Dependent Aβ Pathology in Cynomolgus Monkey Brain

Kimura, Naoko

doi:10.1007/978-981-13-3540-2_7

Cited by 4 publications

(5 citation statements)

References 70 publications

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“…Cornblath and colleagues 43,44 showed reduced motor conduction on aging and the HGM monkey is still at middle age in this study. 20,21 Nonetheless, we have observed a sign of atrophy in AD-specific hippocampus by MRI, coinciding well with large-sample epidemiological investigation in humans. 45 The cognitive deficits may be facilitated by hippocampal insulin resistance through several pathways such as oxidative stress, inflammation, amyloid burden and hypothalamicpituitary-adrenal axis imbalance.…”

Section: Discussionsupporting

confidence: 87%

“…However, it remains unclear whether these biomarkers are sufficient to sustain the AD‐related alterations or cognitive problems. In addition, AD‐related pathology in T2DM cynomolgus monkeys seems dependent on aging and the HGM monkey is still at middle age in this study 20,21 . Nonetheless, we have observed a sign of atrophy in AD‐specific hippocampus by MRI, coinciding well with large‐sample epidemiological investigation in humans 45 .…”

Section: Discussionsupporting

confidence: 81%

“…Macaque monkeys have been found to spontaneously develop various symptoms with aging, such as DM, obesity and AD‐like alterations, making it a fairly suitable for studying the interactions between brain and periphery 20 . In the current study, the HGM monkey presented a string of characteristics highly corresponding to other well‐established diabetic or hyperglycaemic macaque cases and clinical populations.…”

Section: Discussionmentioning

confidence: 78%

“…This study first reported the behavioural alterations, which included decline of specific cognitions and neurological dysfunctions occurring alterations, making it a fairly suitable for studying the interactions between brain and periphery. 20 In the current study, the HGM monkey presented a string of characteristics highly corresponding to other well-established diabetic or hyperglycaemic macaque cases and clinical populations. First of all, we monitored the fluctuation of FPG for consecutive 9 weeks, combining with HbA1c, a gold standard for glycaemic regulation, 22 and evidenced long-term hyperglycaemia.…”

Section: Discussionmentioning

confidence: 79%

“…Significantly, spontaneous NHPs model, in a way, is a more valuable resource for understanding the mechanism and exploring the intervention, because it imitates a natural processes of diabetic or hyperglycaemic in a large proportion of patients and may stabilize the phenotypes once in morbidity. It has been found that spontaneous hyperglycaemic macaques developed nephropathy, 15 retinal denaturation, 16 cardiomyopathy, 17 cardiac dysfunction, 18 α‐synuclein deposition 9 and age‐dependent amyloid‐β (Aβ) pathology, 19–21 which partly is consistent with diabetic or chronic hyperglycaemic patients who may suffer from diabetic kidney disease, diabetic retinopathy, cardiovascular disease, Parkinson's disease (PD) and Alzheimer's disease (AD).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract

Huang,

Pu,

Zhou

et al. 2024

Clin Exp Pharma Physio

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Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non‐human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long‐term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C‐peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes‐like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract

Huang,

Pu,

Zhou

et al. 2024

Clin Exp Pharma Physio

View full text Add to dashboard Cite

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Current state of research on non‐human primate models of Alzheimer’s disease

Zhang

Qin

2019

Anim Models and Exp Med

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With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer's disease (AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non‐human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non‐human primate models of AD was reviewed to provide a theoretical basis for future research.

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Age-, sex- and proximal–distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates

Wang,

Luo,

et al. 2024

Nat Aging

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The incidence of intestinal diseases increases with age, yet the mechanisms governing gut aging and its link to diseases, such as colorectal cancer (CRC), remain elusive. In this study, while considering age, sex and proximal–distal variations, we used a multi-omics approach in non-human primates (Macaca fascicularis) to shed light on the heterogeneity of intestinal aging and identify potential regulators of gut aging. We explored the roles of several regulators, including those from tryptophan metabolism, in intestinal function and lifespan in Caenorhabditis elegans. Suggesting conservation of region specificity, tryptophan metabolism via the kynurenine and serotonin (5-HT) pathways varied between the proximal and distal colon, and, using a mouse colitis model, we observed that distal colitis was more sensitive to 5-HT treatment. Additionally, using proteomics analysis of human CRC samples, we identified links between gut aging and CRC, with high HPX levels predicting poor prognosis in older patients with CRC. Together, this work provides potential targets for preventing gut aging and associated diseases.

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Type II Diabetes Mellitus Accelerates Age-Dependent Aβ Pathology in Cynomolgus Monkey Brain

Cited by 4 publications

References 70 publications

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract

Current state of research on non‐human primate models of Alzheimer’s disease

Age-, sex- and proximal–distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates

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