Article

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

ABSTRACT 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, Aug 10, 2015
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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.
    Journal of Alzheimer's disease: JAD 03/2014; 41(2). DOI:10.3233/JAD-140006 · 4.15 Impact Factor
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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.
    Reviews in the neurosciences 12/2013; 24(6):607-615. DOI:10.1515/revneuro-2013-0034 · 3.31 Impact Factor
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    • "It is worth noting that one of the risk factors for AD is diabetes mellitus, in which excessive generation of free radicals was may play a major pathogenic role (Lipinski, 2001). This has recently resulted in raising intriguing questions regarding the common denominator in AD and diabetes (Craft, 2012; Adeghate et al., 2013; Vignini et al., 2013). Another factor has been suggested to be involved in the pathogenesis of AD, which is copper known to generate hydroxyl radicals in hypoxia. "
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    ABSTRACT: Amyloid hypothesis of Alzheimer's disease (AD) has recently been challenged by the increasing evidence for the role of vascular and hemostatic components that impair oxygen delivery to the brain. One such component is fibrin clots, which, when they become resistant to thrombolysis, can cause chronic inflammation. It is not known, however, why some cerebral thrombi are resistant to the fibrinolytic degradation, whereas fibrin clots formed at the site of vessel wall injuries are completely, although gradually, removed to ensure proper wound healing. This phenomenon can now be explained in terms of the iron-induced free radicals that generate fibrin-like polymers remarkably resistant to the proteolytic degradation. It should be noted that similar insoluble deposits are present in AD brains in the form of aggregates with Abeta peptides that are resistant to fibrinolytic degradation. In addition, iron-induced fibrin fibers can irreversibly trap red blood cells (RBCs) and in this way obstruct oxygen delivery to the brain and induce chronic hypoxia that may contribute to AD. The RBC-fibrin aggregates can be disaggregated by magnesium ions and can also be prevented by certain polyphenols that are known to have beneficial effects in AD. In conclusion, we argue that AD can be prevented by: (1) limiting the dietary supply of trivalent iron contained in red and processed meat; (2) increasing the intake of chlorophyll-derived magnesium; and (3) consumption of foods rich in polyphenolic substances and certain aliphatic and aromatic unsaturated compounds. These dietary components are present in the Mediterranean diet known to be associated with the lower incidence of AD and other degenerative diseases.
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