Central vascular disease and exacerbated pathology in a mixed model of type 2 diabetes and Alzheimer's disease

Ramos-Rodríguez, Juan José; Jiménez-Palomares, Margarita; Murillo‐Carretero, Maribel; Infante-Garcia, Carmen; Berrocoso, Esther; Hernandez-Pacho, Fernando; Lechuga-Sancho, Alfonso M.; Cózar‐Castellano, Irene; García-Alloza, Mónica

doi:10.1016/j.psyneuen.2015.07.606

Cited by 59 publications

(120 citation statements)

References 61 publications

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“…Further assessment of central pathology revealed severe brain atrophy, affecting both cortex and hippocampus in db/db mice (40), while MGF treatment significantly reduced cortical and hippocampal atrophy. As previously described, tau pathology was increased in the cortex and hippocampus from db/db mice (39,40) and hyperphosphorylated tau has also been detected in the pancreas from T2D patients (34). We also detected that NeuN/DAPI ratios were improved after MGF treatment and caspases 3/7 activation was reduced.…”

Section: Discussionsupporting

confidence: 85%

“…Both T1D and T2D mice (39,40), as well as epidemiological studies, link diabetes with vascular disease (2,4). Moreover, people with diabetes have more than double the risk of ischemic stroke and prolonged hyperglycemia is associated with microvascular complications [for review see (30)].…”

Section: Discussionmentioning

confidence: 99%

“…Body weight, postprandial blood glucose and insulin levels were determined immediately before commencing the treatment, at 6 weeks of age, and at 10, 14 and 26 weeks of age as described (39). C-peptide levels were detected in plasma from all groups by ELISA (ALPCO Diagnostic, Salem, NH) following manufacturer's indications.…”

Section: Metabolic Determinationsmentioning

confidence: 99%

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Mango leaf extract improves central pathology and cognitive impairment in a type 2 diabetes mouse model

et al. 2016

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Epidemiological studies reveal that metabolic disorders, and specifically type 2 diabetes (T2D), are relevant risk factors to develop Alzheimer's disease (AD) and vascular dementia (VaD), the most common causes of dementia. AD patients are in a tremendous need of new therapeutic options because of the limited success of available treatments. Natural polyphenols, and concretely Mangifera indica Linn extract (MGF), have been reported to have antiinflammatory, antioxidant and antidiabetic activities. The role of MGF in central complications associated with T2D, after long-term treatment of db/db mice with MGF was analyzed. Metabolic parameters (body weight, glucose and insulin levels) as well as central complications including brain atrophy, inflammatory processes, spontaneous bleeding, tau phosphorylation and cognitive function in db/db mice treated with MGF for 22 weeks were assessed. MGF limits body weight gain in obese db/db mice. Insulin and C-peptide levels, indicative of pancreatic function, were longer maintained in MGF-treated animals. MGF reduced central inflammation by lowering microglia burden, both in the cortex and the hippocampus. Likewise, central spontaneous bleeding was significantly reduced in db/db mice. Cortical and hippocampal atrophy was reduced in db/db mice and tau hyperphosphorylation was lower after MGF treatment, resulting in partial recovery of learning and memory disabilities. Altogether, the data suggested that MGF treatment may provide a useful tool to target different aspects of AD and VaD pathology, and could lead to more effective clinical therapies for the prevention of metabolic related central complications associated with AD and VaD.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Mango leaf extract improves central pathology and cognitive impairment in a type 2 diabetes mouse model

et al. 2016

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“…T2D has also been associated with an increased risk of vascular dementia [25], and pre-diabetic insulin resistance is a risk factor for AD pathology and reduced memory function [26]. Some studies indicate that improving T2D can delay or prevent AD pathology [27]; and therefore, prevention and control of diabetes may reduce the risk of MCI and AD later in life [28]. A significant association between diabetes and AD has also been reported by linking insulin and glucose metabolism load to β-amyloid levels in AD [29].…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

et al. 2017

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BackgroundAssociation of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice.Scope of reviewMetabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues. Mechanistic effect of insulin degrading enzyme (IDE) in decreasing blood glucose and brain Aβ levels will be elucidated. Cyclo-Z effects on these biochemical parameters will be discussed.Major conclusionStimulation of IDE synthesis is effective for the clinical treatment of metabolic diseases including AD and T2D.General significanceCyclo-Z might be the effective treatment of AD and T2D by stimulating IDE synthesis.

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“…Two different patterns of cerebral injury were seen in patients with dementia depending on DM status: greater amyloid plaque load in untreated DM patients but more frequent deep microvascular infarcts in those with treated DM (Sonnen et al 2009). Central vascular disease and exacerbated pathology were seen in a mixed model of DM and AD by crossing APP/PS1 mice (AD model) with db/db mice (DM model) that show an age-dependent synergistic effect between DM and AD, including brain atrophy, senile plaques, hemorrhagic burden, and increase of microglia activation (Ramos-Rodriguez et al 2015). Insulin resistance, hyperinsulinemia, and hyperglycemia can promote the onset of AD (Rönnemaa et al 2008;de Oliveira Lanna et al 2014) by accelerating tau phosphorylation and neuritic plaque formation (Bitel et al 2012;Matsuzaki et al 2010) and, overlapping with AD pathology, aggravate the progression of neurodegeneration due to OS, mitochondrial dysfunction, neuroinflammation, etc.…”

Section: Pathologymentioning

confidence: 99%

The diabetic brain and cognition

et al. 2017

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The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders

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Central vascular disease and exacerbated pathology in a mixed model of type 2 diabetes and Alzheimer's disease

Cited by 59 publications

References 61 publications

Mango leaf extract improves central pathology and cognitive impairment in a type 2 diabetes mouse model

Mango leaf extract improves central pathology and cognitive impairment in a type 2 diabetes mouse model

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

The diabetic brain and cognition

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