Association between the characteristics of metabolic syndrome and Alzheimer’s disease

Abstract

Various epidemiological studies have shown that type 2 diabetes and metabolic syndrome are highly correlated with Alzheimer's disease (AD). Here, we sought to assess the impact of metabolic syndrome characteristics on the progression of AD. Five-week-old male, spontaneously hypertensive (n = 32) and Wistar Kyoto (abbreviated WKY; n = 8) rats were divided into 5 groups (each n = 8): WKY, hypertension (HTN), streptozotocin-induced diabetes (STZ), high-fat diet (HFD), and STZ + high-fat diet-induced diabetes mellitus (DM). All animals were sacrificed and samples of the blood, liver, and brain were collected for further biological analysis. During the 15-week period of induction, the STZ and DM groups (animals injected with low-dose STZ) had significantly higher fasting glucose levels; the HFD group had elevated insulin levels, but normal blood glucose levels. The HFD and DM groups had hypercholesterolemia and higher hepatic levels of triglycerides and cholesterol. Additionally, correlations between HFD and elevated brain amyloid-beta 42 (Aβ-42), hyperglycemia and down-regulation of brain insulin receptor, and serum Aβ-42 and hepatic triglyceride concentrations (r(2) = 0.41, p < 0.05) were observed. Serum C-reactive protein and malondialdehyde did not appear to have a significant influence on the association with biomarkers of AD. Thus, our study demonstrated that rats with characteristics of metabolic syndrome had a large number of biomarkers predicting AD; however, no relationship between traditional inflammatory and oxidative markers and AD was found. Further studies are necessary to prove that these findings in rats are relevant to AD processes in humans.

Is Alzheimer’s Disease a Liver Disease of the Brain?

“…In murine models, correlations between a high fat diet and elevated brain and serum A␤ 42 have been observed [122], and NALFD induces signs of AD in wild-type mice and accelerates pathological signs of AD [123]. Advanced glycation end-products exacerbate progression of experimental NAFLD [124] and AD [22].…”

Obesity and sex interact in the regulation of Alzheimer's disease

“…For example, the BBZDR/Wor rats, a strain genetically prone to T2D, have greater neuronal loss and Aβ pathology than do BB/Wor rats, which are genetically prone to Type 1 diabetes (Li et al, 2007) Further, treatment with streptozotocin (STZ), which kills pancreatic β-cells, is commonly used to induce type I diabetes in animal models. STZ has been found to increase Aβ in both mouse (Currais et al, 2012; Jolivalt et al, 2008; Wang et al, 2010) and rat (Yang et al, 2013) models, as well as increase tau phosphorylation in brain (Jolivalt et al, 2008; Kim et al, 2009; Planel et al, 2007). Transgenic mouse models of obesity include leptin deficient mice (ob/ob) and leptin receptor deficient mice (db/db).…”

Maternal high-fat diet alters expression of pathways of growth, blood supply and arachidonic acid in rat placenta

“…The Alzheimer's disease pathway encompasses many cellular processes including receptor signalling, oxidative phosphorylation and Ca signalling, which all lead to apoptosis. Alzheimer's disease has been associated with the metabolic syndrome in humans ( 14 ) and Wistar Kyoto rats fed a HFD show increases in the levels of biomarkers for Alzheimer's disease ( 15 ) . Apoptosis was one of the main pathways that we reported for the analysis with all genes that were differentially expressed in the placentae of dams on the HFD or the control diet.…”