TY - JOUR
T1 - Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease
T2 - Testosterone as a Modifier
AU - Asih, Prita R.
AU - Tegg, Michelle L.
AU - Sohrabi, Hamid
AU - Carruthers, Malcolm
AU - Gandy, Samuel E.
AU - Saad, Farid
AU - Verdile, Giuseppe
AU - Ittner, Lars M.
AU - Martins, Ralph N.
PY - 2017
Y1 - 2017
N2 - 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-beta(A beta) 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 cerebral A beta deposition in T2DM, the extent of A beta accumulation in AD correlates withT2DMduration. 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.
AB - 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-beta(A beta) 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 cerebral A beta deposition in T2DM, the extent of A beta accumulation in AD correlates withT2DMduration. 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.
KW - Alzheimer's disease
KW - men
KW - testosterone
KW - type-2 diabetes
KW - women
KW - INSULIN-DEGRADING ENZYME
KW - C-REACTIVE PROTEIN
KW - ANDROGEN-DEPRIVATION THERAPY
KW - APOLIPOPROTEIN-E GENOTYPE
KW - SEX STEROID-HORMONES
KW - GROWTH-FACTOR-I
KW - GLYCOGEN-SYNTHASE KINASE-3
KW - MESSENGER-RNA EXPRESSION
KW - AMYLOID BETA-PROTEIN
KW - METABOLIC SYNDROME
U2 - 10.3233/JAD-161259
DO - 10.3233/JAD-161259
M3 - Review article
C2 - 28655134
VL - 59
SP - 445
EP - 466
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 2
ER -