Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier

Evidence in support of links between type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has increased considerably in recent years. AD pathological hallmarks include the accumulation of extracellular amyloid-ß (Aß) and intracellular hyperphosphorylated tau in the brain, which are hypo...

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Main Authors: Asih, P., Tegg, M., Sohrabi, H., Carruthers, M., Gandy, S., Saad, F., Verdile, Giuseppe, Ittner, L., Martins, R.
Format: Journal Article
Published: IOS Press 2017
Online Access:http://hdl.handle.net/20.500.11937/56666
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author Asih, P.
Tegg, M.
Sohrabi, H.
Carruthers, M.
Gandy, S.
Saad, F.
Verdile, Giuseppe
Ittner, L.
Martins, R.
author_facet Asih, P.
Tegg, M.
Sohrabi, H.
Carruthers, M.
Gandy, S.
Saad, F.
Verdile, Giuseppe
Ittner, L.
Martins, R.
author_sort Asih, P.
building Curtin Institutional Repository
collection Online Access
description Evidence in support of links between type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has increased considerably in recent years. AD pathological hallmarks include the accumulation of extracellular amyloid-ß (Aß) and intracellular hyperphosphorylated tau in the brain, which are hypothesized to promote inflammation, oxidative stress, and neuronal loss. T2DM exhibits many AD pathological features, including reduced brain insulin uptake, lipid dysregulation, inflammation, oxidative stress, and depression; T2DM has also been shown to increase AD risk, and with increasing age, the prevalence of both conditions increases. In addition, amylin deposition in the pancreas is more common in AD than in normal aging, and although there is no significant increase in cer ebral Aß deposition in T2DM, the extent of Aß accumulation in AD correlates with T2DM duration. Given these similarities and correlations, there may be common underlying mechanism(s) that predispose to both T2DM and AD. In other studies, an age-related gradual loss of testosterone and an increase in testosterone resistance has been shown in men; low testosterone levels can also occur in women. In this review, we focus on the evidence for low testosterone levels contributing to an increased risk of T2DM and AD, and the potential of testosterone treatment in reducing this risk in both men and women. However, such testosterone treatment may need to be long-term, and would need regular monitoring to maintain testosterone at physiological levels. It is possible that a combination of testosterone therapy together with a healthy lifestyle approach, including improved diet and exercise, may significantly reduce AD risk.
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spelling curtin-20.500.11937-566662018-02-12T03:57:14Z Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier Asih, P. Tegg, M. Sohrabi, H. Carruthers, M. Gandy, S. Saad, F. Verdile, Giuseppe Ittner, L. Martins, R. Evidence in support of links between type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has increased considerably in recent years. AD pathological hallmarks include the accumulation of extracellular amyloid-ß (Aß) and intracellular hyperphosphorylated tau in the brain, which are hypothesized to promote inflammation, oxidative stress, and neuronal loss. T2DM exhibits many AD pathological features, including reduced brain insulin uptake, lipid dysregulation, inflammation, oxidative stress, and depression; T2DM has also been shown to increase AD risk, and with increasing age, the prevalence of both conditions increases. In addition, amylin deposition in the pancreas is more common in AD than in normal aging, and although there is no significant increase in cer ebral Aß deposition in T2DM, the extent of Aß accumulation in AD correlates with T2DM duration. Given these similarities and correlations, there may be common underlying mechanism(s) that predispose to both T2DM and AD. In other studies, an age-related gradual loss of testosterone and an increase in testosterone resistance has been shown in men; low testosterone levels can also occur in women. In this review, we focus on the evidence for low testosterone levels contributing to an increased risk of T2DM and AD, and the potential of testosterone treatment in reducing this risk in both men and women. However, such testosterone treatment may need to be long-term, and would need regular monitoring to maintain testosterone at physiological levels. It is possible that a combination of testosterone therapy together with a healthy lifestyle approach, including improved diet and exercise, may significantly reduce AD risk. 2017 Journal Article http://hdl.handle.net/20.500.11937/56666 10.3233/JAD-161259 IOS Press restricted
spellingShingle Asih, P.
Tegg, M.
Sohrabi, H.
Carruthers, M.
Gandy, S.
Saad, F.
Verdile, Giuseppe
Ittner, L.
Martins, R.
Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier
title Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier
title_full Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier
title_fullStr Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier
title_full_unstemmed Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier
title_short Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier
title_sort multiple mechanisms linking type 2 diabetes and alzheimer's disease: testosterone as a modifier
url http://hdl.handle.net/20.500.11937/56666