Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Erythrocytes as Potential Link between Diabetes and Alzheimer's Disease.

ABSTRACT: Many studies support the existence of an association between type 2 diabetes (T2DM) and Alzheimer's disease (AD). In AD, in addition to brain, a number of peripheral tissues and cells are affected, including red blood cell (RBC) and because there are currently no reliable diagnostic biomarkers of AD in the blood, a gradually increasing attention has been given to the study of RBC's alterations. Recently it has been evidenced in diabetes, RBC alterations superimposable to the ones occurring in AD RBC. Furthermore, growing evidence suggests that oxidative stress plays a pivotal role in the development of RBC's alterations and vice versa. Once again this represents a further evidence of a shared pathway between AD and T2DM. The present review summarizes the two disorders, highlighting the role of RBC in the postulated common biochemical links, and suggests RBC as a possible target for clinical trials.

SUBMITTER: Carelli-Alinovi C

PROVIDER: S-EPMC5574872 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Erythrocytes as Potential Link between Diabetes and Alzheimer's Disease.

Carelli-Alinovi Cristiana C Misiti Francesco F

Frontiers in aging neuroscience 20170825

Many studies support the existence of an association between type 2 diabetes (T2DM) and Alzheimer's disease (AD). In AD, in addition to brain, a number of peripheral tissues and cells are affected, including red blood cell (RBC) and because there are currently no reliable diagnostic biomarkers of AD in the blood, a gradually increasing attention has been given to the study of RBC's alterations. Recently it has been evidenced in diabetes, RBC alterations superimposable to the ones occurring in AD ...[more]

PMID: 28890694

Similar Datasets

Link between type 2 diabetes and Alzheimer's disease: from epidemiology to mechanism and treatment.

Project description:The aim of this paper is to provide a comprehensive review of the epidemiological evidence linking type 2 diabetes mellitus and its related conditions, including obesity, hyperinsulinemia, and metabolic syndrome, to Alzheimer's disease (AD). Several mechanisms could help to explain this proposed link; however, our focus is on insulin resistance and deficiency. Studies have shown that insulin resistance and deficiency can interact with amyloid-β protein and tau protein phosphorylation, each leading to the onset and development of AD. Based on those epidemiological data and basic research, it was recently proposed that AD can be considered as "type 3 diabetes". Special attention has been paid to determining whether antidiabetic agents might be effective in treating AD. There has been much research both experimental and clinical on this topic. We mainly discuss the clinical trials on insulin, metformin, thiazolidinediones, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors in the treatment of AD. Although the results of these trials seem to be contradictory, this approach is also full of promise. It is worth mentioning that the therapeutic effects of these drugs are influenced by the apolipoprotein E (APOE)-ε4 genotype. Patients without the APOE-ε4 allele showed better treatment effects than those with this allele.

| S-EPMC4360697 | biostudies-literature

The link between chronic pain and Alzheimer's disease.

Project description:Chronic pain often occurs in the elderly, particularly in the patients with neurodegenerative disorders such as Alzheimer's disease (AD). Although studies indicate that chronic pain correlates with cognitive decline, it is unclear whether chronic pain accelerates AD pathogenesis. In this review, we provide evidence that supports a link between chronic pain and AD and discuss potential mechanisms underlying this connection based on currently available literature from human and animal studies. Specifically, we describe two intertwined processes, locus coeruleus noradrenergic system dysfunction and neuroinflammation resulting from microglial pro-inflammatory activation in brain areas mediating the affective component of pain and cognition that have been found to influence both chronic pain and AD. These represent a pathological overlap that likely leads chronic pain to accelerate AD pathogenesis. Further, we discuss potential therapeutic interventions targeting noradrenergic dysfunction and microglial activation that may improve patient outcomes for those with chronic pain and AD.

| S-EPMC6836339 | biostudies-literature

Hyperglycemia-induced tau cleavage in vitro and in vivo: a possible link between diabetes and Alzheimer's disease.

Project description:Multiple lines of evidence link the incidence of diabetes to the development of Alzheimer's disease (AD). Patients with diabetes have a 50 to 75% increased risk of developing AD. In parallel, AD patients have a higher than normal tendency to develop type 2 diabetes or impaired fasting glucose. Tau is the major component of neurofibrillary tangles, one of the hallmarks of AD pathology. The current study examined the effect of hyperglycemia on tau modification. Glucose treatment of rat embryonic cortical neurons results in concentration-dependent apoptosis and caspase-3 activation. These changes are well correlated with glucose time- and concentration-dependent tau cleavage. Aβ treatment induces tau cleavage and when added together with glucose, there is an additive effect on caspase activation, apoptosis, and tau cleavage. Tau cleavage is partially blocked by the caspase inhibitor, ZVAD. Cleaved tau displays a punctate staining along the neurites and colocalizes with cleaved caspase-3 in the cytoplasm. Both type 1 and type 2 diabetic mice display increased tau phosphorylation in the brain. In agreement with the effects of glucose on tau modifications in vitro, there is increased tau cleavage in the brains of ob/ob mice; however, tau cleavage is not observed in type 1 diabetic mouse brains. Our study demonstrates that hyperglycemia is one of major factors that induce tau modification in both in vitro and in vivo models of diabetes. We speculate that tau cleavage in diabetic conditions (especially in type 2 diabetes) may be a key link for the increased incidence of AD in diabetic patients.

| S-EPMC5545747 | biostudies-other

Inflammation: the link between comorbidities, genetics, and Alzheimer's disease.

Project description:Alzheimer's disease (AD) is a neurodegenerative disorder, most cases of which lack a clear causative event. This has made the disease difficult to characterize and, thus, diagnose. Although some cases are genetically linked, there are many diseases and lifestyle factors that can lead to an increased risk of developing AD, including traumatic brain injury, diabetes, hypertension, obesity, and other metabolic syndromes, in addition to aging. Identifying common factors and trends between these conditions could enhance our understanding of AD and lead to the development of more effective treatments. Although the immune system is one of the body's key defense mechanisms, chronic inflammation has been increasingly linked with several age-related diseases. Moreover, it is now well accepted that chronic inflammation has an important role in the onset and progression of AD. In this review, the different inflammatory signals associated with AD and its risk factors will be outlined to demonstrate how chronic inflammation may be influencing individual susceptibility to AD. Our goal is to bring attention to potential shared signals presented by the immune system during different conditions that could lead to the development of successful treatments.

| S-EPMC6154824 | biostudies-literature

Unraveling the link: exploring the causal relationship between diabetes, multiple sclerosis, migraine, and Alzheimer's disease through Mendelian randomization.

Project description:IntroductionObservational studies suggested that diabetes mellitus [type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM)], multiple sclerosis (MS), and migraine are associated with Alzheimer's disease (AD). However, the causal link has not been fully elucidated. Thus, we aim to assess the causal link between T1DM, T2DM, MS, and migraine with the risk of AD using a two-sample Mendelian randomization (MR) study.MethodsGenetic instruments were identified for AD, T1DM, T2DM, MS, and migraine respectively from genome-wide association study. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method.ResultsThe result of IVW method demonstrated that T2DM is causally associated with risk of AD (OR: 1.237, 95% CI: 1.099-1.391, P: 0.0003). According to the IVW method, there is no causal association between TIDM, MS, migraine, and the risk of AD (all p value > 0.05). Here we show, there is a causal link between T2DM and the risk of AD.ConclusionThese findings highlight the significance of active monitoring and prevention of AD in T2DM patients. Further studies are required to actively search for the risk factors of T2DM combined with AD, explore the markers that can predict T2DM combined with AD, and intervene and treat early.

| S-EPMC10488716 | biostudies-literature

Amylin-Aβ oligomers at atomic resolution using molecular dynamics simulations: a link between Type 2 diabetes and Alzheimer's disease.

Project description:Clinical studies have identified Type 2 diabetes (T2D) as a risk factor of Alzheimer's disease (AD). One of the potential mechanisms that link T2D and AD is the loss of cells associated with degenerative changes. Amylin1-37 aggregates (the pathological species in T2D) were found to be co-localized with those of Aβ1-42 (the pathological species in AD) to form the Amylin1-37-Aβ1-42 plaques, promoting aggregation and thus contributing to the etiology of AD. However, the mechanisms by which Amylin1-37 co-aggregates with Aβ1-42 are still elusive. This work presents the interactions between Amylin1-37 oligomers and Aβ1-42 oligomers at atomic resolution applying extensive molecular dynamics simulations for relatively large ensemble of cross-seeding Amylin1-37-Aβ1-42 oligomers. The main conclusions of this study are first, Aβ1-42 oligomers prefer to interact with Amylin1-37 oligomers to form single layer conformations (in-register interactions) rather than double layer conformations; and second, in some double layer conformations of the cross-seeding Amylin1-37-Aβ1-42 oligomers, the Amylin1-37 oligomers destabilize the Aβ1-42 oligomers and thus inhibit Aβ1-42 aggregation, while in other double layer conformations, the Amylin1-37 oligomers stabilize Aβ1-42 oligomers and thus promote Aβ1-42 aggregation.

| S-EPMC4720542 | biostudies-literature

Amylin-Aβ oligomers at atomic resolution using molecular dynamics simulations: a link between Type 2 diabetes and Alzheimer's disease.

| S-EPMC4720542 | biostudies-literature

Evaluating the link between Paraoxonase-1 levels and Alzheimer's disease development.

Project description:At present, the etiopathogenesis of Alzheimer's disease (AD), the most common form of dementia, remains far to be fully deciphered. In the recent years, also the centrality of amyloid-β peptide in the pathogenesis of the neurodegenerative disease has been questioned and other hypotheses have been advanced. Notably, a common denominator of many of these theoretical models is represented by oxidative stress, which is widely proposed to play a role in the disease initiation and/or progression. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme that endows its carrier with multiple biological functions, including the ability to contrast oxidative damage to lipid components of lipoproteins and cells and protect from toxicity of specific organophosphorus pesticides. The peculiar multi-functionality nature of PON1 might be the key for explaining the vast epidemiological data showing a close association between low serum PON1 activity and risk of several diseases, including cardiovascular and neurodegenerative diseases, in particular AD. In this review, we discuss the possible link between PON1 with AD pathogenesis and we hypothesize eventual mechanistic pathways that could account from epidemiological observations. We also highlight the methodological issue limitation in PON1 studies that still impede to give a definitive and certain picture of its effective biological impact on human health including AD.

| S-EPMC7451062 | biostudies-literature

Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and A? generation in Alzheimer's disease.

Project description:BackgroundOne of the best-characterized causative factors of Alzheimer's disease (AD) is the generation of amyloid-? peptide (A?). AD subjects are at high risk of epileptic seizures accompanied by aberrant neuronal excitability, which in itself enhances A? generation. However, the molecular linkage between epileptic seizures and A? generation in AD remains unclear.ResultsX11 and X11-like (X11L) gene knockout mice suffered from epileptic seizures, along with a malfunction of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Genetic ablation of HCN1 in mice and HCN1 channel blockage in cultured Neuro2a (N2a) cells enhanced A? generation. Interestingly, HCN1 levels dramatically decreased in the temporal lobe of cynomolgus monkeys (Macaca fascicularis) during aging and were significantly diminished in the temporal lobe of sporadic AD patients.ConclusionBecause HCN1 associates with amyloid-? precursor protein (APP) and X11/X11L in the brain, genetic deficiency of X11/X11L may induce aberrant HCN1 distribution along with epilepsy. Moreover, the reduction in HCN1 levels in aged primates may contribute to augmented A? generation. Taken together, HCN1 is proposed to play an important role in the molecular linkage between epileptic seizures and A? generation, and in the aggravation of sporadic AD.

| S-EPMC3524764 | biostudies-literature

Investigating a Genetic Link Between Alzheimer's Disease and CADASIL-Related Cerebral Small Vessel Disease.

Project description:Monogenic forms of Alzheimer's disease (AD) have been identified through mutations in genes such as APP, PSEN1, and PSEN2, whilst other genetic markers such as the APOE ε carrier allele status have been shown to increase the likelihood of having the disease. Mutations in these genes are not limited to AD, as APP mutations can also cause an amyloid form of cerebral small vessel disease (CSVD) known as cerebral amyloid angiopathy, whilst PSEN1 and PSEN2 are involved in NOTCH3 signalling, a process known to be dysregulated in the monogenic CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The overlap between AD genes and causes of CSVD led to the hypothesis that mutations in other genes within the PANTHER AD-presenilin pathway may be novel causes of CSVD in a cohort of clinically suspicious CADASIL patients without a pathogenic NOTCH3 mutation. To investigate this, whole exome sequencing was performed on 50 suspected CADASIL patients with no NOTCH3 mutations, and a targeted gene analysis was completed on the PANTHER. ERN1 was identified as a novel candidate CSVD gene following predicted pathogenic gene mutation analysis. Rare variant burden testing failed to identify an association with any gene; however, it did show a nominally significant link with ERN1 and TRPC3. This study provides evidence to support a genetic overlap between CSVD and Alzheimer's disease.

| S-EPMC9616771 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data