Mechanisms linking brain insulin resistance to Alzheimer's disease

Matioli, Maria Niures P.S.; Nitrini, Ricardo

doi:10.1590/1980-57642015dn92000003

Cited by 42 publications

(17 citation statements)

References 90 publications

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“…Elevations of t-Tau and p-Tau in the CSF are biomarkers of tauopathy in AD and they correlated well with intracerebral AD pathology, while decreases of Aβ1-42 in the CSF are inversely proportional to amyloid in the brain (Reitz, 2012 ). There is also an increasing evidence that patients with diabetes shared commonality with neuropathology in AD (Matioli and Nitrini, 2015 ). Moreover, the risk of AD has also been shown to be increased in prediabetes individuals with high fasting glucose and/or impaired glucose tolerance due to IR and simultaneous exposure to abnormally high levels of insulin persisting for extended periods of time (hyperinsulinemia) (Roriz-Filhom et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Changes in Cerebrospinal Fluid Tau and β-Amyloid Levels in Diabetic and Prediabetic Patients: A Meta-Analysis

Jiang

Liu

et al. 2018

Front. Aging Neurosci.

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Increased risks for Alzheimer's disease (AD) are a well-recognized consequence of diabetes, insulin resistance (IR), and hyperinsulinemia. Since cerebrospinal fluid (CSF) is surrounding the central nervous system, alterations of β-amyloid (Aβ) and tau protein in the CSF may be indicative of AD-type degenerations in the brain. Current laboratory diagnosis of AD uses three biomarkers in CSF: Aβ1-42, total tau (t-Tau), and phosphorylated tau (p-Tau). However, changes in these biomarkers in diabetic and prediabetic patients are scattered and variable in literature. Thus, we attempt to perform a systematical analysis of these available data. MEDLINE, EMBASE, the Cochrane Central database, China National Knowledge Infrastructure (CNKI), and Wanfang Data electronic databases were searched to gather published studies that have evaluated the AD-type biomarkers in the CSF of subjects with diabetes, IR, or hyperinsulinemia in comparison with respective controls. Overall analysis of the published data showed no significant differences in Aβ1-42, t-Tau, and p-Tau levels in the CSF between the (pre)diabetic subjects and controls. However, subgroup analysis suggested that (pre)diabetic conditions might accelerate decrease of Aβ1-42, but increase of t-Tau levels in the CSF of subjects with cognitive impairment, and the association with p-Tau in the CSF was stronger (P = 0.001) for diabetes than those of prediabetes (P = 0.61). Our analyses reveal that the relationship between (pre)diabetic conditions and AD-type biomarker status in the CSF was subjective to clinical characteristics.

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Section: Introductionmentioning

confidence: 99%

Changes in Cerebrospinal Fluid Tau and β-Amyloid Levels in Diabetic and Prediabetic Patients: A Meta-Analysis

Jiang

Liu

et al. 2018

Front. Aging Neurosci.

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“…BACE 1 is a rate-limiting enzyme in the cleavage of the APP to Aβ peptides (Durairajan et al, 2017), and IDE is a major endogenous Aβ-degrading enzyme. The levels and enzymatic activity of IDE are negatively correlated with the size of the amyloid plaques and AD pathology (Matioli and Nitrini, 2015). To investigate the effects of ADH1B on these proteins (p75NTR, BACE 1, and IDE) related to Aβ1-42 metabolism, we established ADH1B-overexpression and ADH1B-shRNA lentiviral vectors.…”

Section: Resultsmentioning

confidence: 99%

Alcohol Dehydrogenase 1B Suppresses β-Amyloid-Induced Neuron Apoptosis

Wang

Zhang

et al. 2019

Front. Aging Neurosci.

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β-amyloid (Aβ) deposition, neurofibrillary tangles induced by phosphorylation of tau protein, and neuronal apoptosis are pathological hallmarks of Alzheimer’s disease (AD). The dementia rate in alcoholic abusers were found to be higher than in control people. The present study explored the potential roles of alcohol dehydrogenase 1B (ADH1B) in AD pathology by determining the ADH1B levels in AD patient sera, in the hippocampus of APP/PS-1 AD model mice, and in an AD model cell line treated with Aβ1-42. The results show that ADH1B levels decreased significantly both in the serum of AD patients and in the hippocampus of APP/PS-1 AD model mice. In addition, the apoptotic rate was reduced and viability was significantly increased in AD model cells transfected with ADH1B overexpression vector. The levels of the p75 neurotrophin receptor (p75NTR), an Aβ1-42 receptor, were down-regulated in the ADH1B overexpressing AD model cell and up-regulated in cells transfected with the shRNA vector of ADH1B. Protein levels of cleaved caspase-3 and Bax decreased significantly, whereas Bcl-2 levels increased in cells overexpressing ADH1B. The opposite trend was observed for cleaved caspase-3, Bax, and Bcl-2 levels in cells transfected with the shRNA vector of ADH1B. The levels of reactive oxygen species (ROS) were found to be reduced in ADH1B overexpressing cells and increased when cells were transfected with the shRNA vector of ADH1B. These results indicate that ADH1B might be important in the prevention of AD, especially for abusers of alcohol, and a potential new target of AD treatment.

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“…Insulin resistance in type 2 diabetes and obesity is a critical factor driving cognitive decline, especially in verbal memory, learning, and mental speed, suggesting that chronic areca nut consumption also could be associated with cognitive impairment [ 151 , 152 , 153 ]. Recent studies of addiction revealed morphological, functional, metabolic, and behavioral impairments in areca-nut-dependent users, including chronic deficits in spatial memory [ 154 ].…”

Section: The Rising Tide Of Insulin Resistance Diseases and Cognimentioning

confidence: 99%

Betel Quid Health Risks of Insulin Resistance Diseases in Poor Young South Asian Native and Immigrant Populations

Moriel

Lin

Tanoukhy

et al. 2020

IJERPH

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Betel quid, traditionally prepared with areca nut, betel leaf, and slaked lime, has been consumed for thousands of years, mainly in the form of chewing. Originally used for cultural, medicinal, and ceremonial purposes mainly in South Asian countries, its use has recently spread across the globe due to its psychoactive, euphoric, and aphrodisiac properties. Now it is widely used as a social lubricant and source of financial profit. Unfortunately, the profit motive has led to high rates of habitual consumption with eventual conversion to addiction among young girls and boys. Moreover, the worrisome practice of including tobacco in quid preparations has grown, particularly among pregnant women. Major health concerns include increased rates of malignancy, oral pathology, and cardiovascular, hepatic, fertility, metabolic, and neuropsychiatric disorders. Metabolic disorders and insulin resistance disease states such as type 2 diabetes, obesity, and metabolic syndrome contribute to cognitive decline and neurodegeneration. Mechanistically, the constituents of areca nut/betel quid are metabolized to N-nitroso compounds, i.e., nitrosamines, which are carcinogenic at high doses and cause insulin resistance following chronic low-level exposures. From an epidemiological perspective, the rising tide of insulin resistance diseases including obesity, diabetes, and dementias that now disproportionately burden poor countries has been propagated by rapid commercialization and enhanced access to betel quid. Public health measures are needed to impose socially and ethically responsible barriers to yet another cause of global health disparity.

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Mechanisms linking brain insulin resistance to Alzheimer's disease

Cited by 42 publications

References 90 publications

Changes in Cerebrospinal Fluid Tau and β-Amyloid Levels in Diabetic and Prediabetic Patients: A Meta-Analysis

Changes in Cerebrospinal Fluid Tau and β-Amyloid Levels in Diabetic and Prediabetic Patients: A Meta-Analysis

Alcohol Dehydrogenase 1B Suppresses β-Amyloid-Induced Neuron Apoptosis

Betel Quid Health Risks of Insulin Resistance Diseases in Poor Young South Asian Native and Immigrant Populations

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