Alzheimer's disease And Diabetes: New Insights and Unifying Therapies.

Department of Clinical Science, Section of Biochemistry, School of Medicine. Università Politecnica delle Marche, Via Tronto 10 A, 60020 Ancona, Italy. .
Current diabetes reviews 01/2013; 9(3). DOI: 10.2174/1573399811309030003
Source: PubMed


Several research groups have begun to associate the Alzheimer Disease (AD) to Diabetes Mellitus (DM), obesity and cardiovascular disease. This relationship is so close that some authors have defined Alzheimer Disease as Type 3 Diabetes. Numerous studies have shown that people with type 2 diabetes have twice the incidence of sporadic AD. Insulin deficiency or insulin resistance facilitates cerebral β-amyloidogenesis in murine model of AD, accompanied by a significant elevation in APP (Amyloid Precursor Protein) and BACE1 (β-site APP Cleaving Enzime 1). Similarly, deposits of Aβ produce a loss of neuronal surface insulin receptors and directly interfere with the insulin signaling pathway. Furthermore, as it is well known, these disorders are both associated to an increased cardiovascular risk and an altered cholesterol metabolism, so we have analyzed several therapies which recently have been suggested as a remedy to treat together AD and DM. The aim of the present review is to better understand the strengths and drawbacks of these therapies.

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Available from: Arianna Vignini
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    • "A potential limitation of this approach is the ambulatory surgery required for the implant and replacement of this device [143]. Nevertheless, it may help enhance adherence not only in diabetic patients but in diabetic patients with neurodegenerative diseases [144]. Despite recent innovations for injectables, the oral route of administration remains the most widely accepted [145] and will need to be considered together with the safety and efficacy profile for the success of new GLP-1 based therapies. "
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    ABSTRACT: Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) resulting in superior body weight lowering to selective GLP1R agonists. OXM reduces food intake and increases energy expenditure in humans. While activation of the GCGR increases glucose production posing a hyperglycemic risk, the simultaneous activation of the GLP1R counteracts this effect. Acute OXM infusion improves glucose tolerance in T2DM patients making dual agonists of the GCGR and GLP1R new promising treatments for diabetes and obesity with the potential for weight loss and glucose lowering superior to that of GLP1R agonists.
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    • "Likewise, the blockers of renin-angiotensin system alter the serum levels of adipokines, affect insulin resistance, and slow down the decline of cognition in AD subjects [41]. Several other drugs affecting glucose homeostasis and insulin resistance like metformin, thiazolinediones, and GLP-1 (glucagon like peptide-1) agonists may become potential candidates for the treatment of AD with or without diabetes [42] [43]. "
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    ABSTRACT: Cerebral hypometabolism of glucose, weight loss, and decreased food intake are characteristic features of sporadic Alzheimer's disease (AD). A systematic study on the serum levels of adipokines and insulin, the major hormones regulating energy metabolism, food intake, and body weight, in sporadic AD is necessary. The present study compares the serum levels of leptin, adiponectin, and insulin, measured by commercially available immuno-assay kits, between controls and sporadic AD subjects. The results show a conspicuous decrease in the level of leptin, a dramatic rise in the level of adiponectin, and also a statistically significant increase in insulin level, in the blood of AD subjects, with respect to controls. The changes in the serum levels of adiponectin and insulin in AD are positively correlated with the severity of dementia. Likewise, the serum level of leptin in AD subjects is negatively correlated with the degree of dementia. The changes in the levels of adipokines and insulin have implications in the amyloid pathology, neurodegeneration, and hypometabolism of glucose existing in the AD brain.
    No preview · Article · Mar 2014 · Journal of Alzheimer's disease: JAD
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    • "Thus, most studies on AD research depend on transgenic models only mutant on APP, PS1 and tau. However, an increasing number of factors, including ApoE4, oxidative stress, aging and insulin resistance, have been found to be related to AD, especially late-onset ( > 60 years) or sporadic AD (Liu et al., 2013; Schraml et al., 2013; Vignini et al., 2013). The investigation of the insulin desensitization in the brains of AD patients adds new information about the progression and origin of the disease. "
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    ABSTRACT: Abstract Alzheimer's disease (AD) is a complex neurodegenerative disorder, which involves many underlying pathological processes. Recently, it has been demonstrated that AD also includes impairments of insulin signaling in the brain. Type 2 diabetes is a risk factor for AD, and AD and diabetes share a number of pathologies. The classical hallmarks of AD are senile plaques and neurofibrillary tangles, which consist of amyloid-β and hyperphosphorylated tau. Based on the two hallmarks, transgenic animal models of AD have been developed, which express mutant human genes of amyloid precursor protein, presenilin-1/2, and tau. It is likely that these mouse models are too limited in their pathology. In this work, we describe mouse models that model diabetes and show insulin signaling impairment as well as neurodegenerative pathologies that are similar to those seen in the brains of AD patients. The combination of traditional AD mouse models with induced insulin impairments in the brain may be a more complete model of AD. Interestingly, AD mouse models treated with drugs that have been developed to cure type 2 diabetes have shown impressive outcomes. Based on these findings, several ongoing clinical trials are testing long lasting insulin analogues or GLP-1 mimetics in patients with AD.
    Full-text · Article · Dec 2013 · Reviews in the neurosciences
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