Occurrence Of Alzheimer's Disease Research Articles

Current nursing status of diabetes mellitus with alzheimer’s disease

The occurrence of alzheimer's disease is closely related to diabetes.When diabetic patients suffer from long-term poor blood glucose control, repeated hypoglycemia and other problems, central nervous system and cerebrovascular diseases will occur, accelerating the occurrence of alzheimer's disease.In this paper, the current and effective nursing interventions for diabetes mellitus with alzheimer's disease were summarized to reduce the incidence of complications and improve the quality of life of patients. Key words: Diabetic mellitus; Alzheimer's disease; Current nursing status

VACCINATION AGAINST PNEUMONIA IN THE ELDERLY MAY REDUCE ALZHEIMER’S RISK

Accumulating evidence suggests that infections may contribute to Alzheimer's disease (AD) development. Various pathogens were considered in this regard, indicating a possibility that compromised host ability to respond to infection may play major role in this connection. Few studies, however, tested interventions that may improve the immune response to infection and overall robustness/ resilience of the immune system, and through this protect against AD. One such candidate intervention could be pneumonia vaccine that has been shown to have a broad effect on morbidity and mortality in the elderly in several studies. We investigated the impact of the vaccination against pneumonia (with and without an accompanying flu shot) between ages 65 and 75, on the risk of AD occurrence after age 75, in elderly (65+) participants of the Cardiovascular Health Study (CHS), using both logistic and Cox models. We found that individuals, who were vaccinated against both pneumonia and flu before the age 75, had significantly decreased chances of AD occurrence between ages 75 and 85 in logistic model (p-value=5E-06; OR=0.43). People who had pneumonia vaccination without flu shot before the age 75 also had significantly decreased risk of AD after the age 75, though less prominently (p-value=0.01; OR=0.67). Analysis, using Cox model supported these findings. Vaccination against pneumonia (alone or together with flu shot) could be a promising new candidate for repurposing in AD prevention, potentially acting through improving resilience of the immune system in the elderly. Further testing and validation of these effects in other human data is warranted. The study was supported by NIH grants R56AG059428 and R01AG046860.

The db mutation improves memory in younger mice in a model of Alzheimer's disease

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease, while obesity is a major global public health problem associated with the metabolic disorder type 2 diabetes mellitus (T2DM). Chronic obesity and T2DM have been identified as invariant risk factors for dementia and late-onset AD, while their impacts on the occurrence and development of AD remain unclear. As shown in our previous study, the diabetic mutation (db, Leprdb/db) induces mixed or vascular dementia in mature to middle-aged APPΔNL/ΔNL x PS1P264L/P264L knock-in mice (db/AD). In the present study, the impacts of the db mutation on young AD mice at 10 weeks of age were evaluated. The db mutation not only conferred young AD mice with severe obesity, impaired glucose regulation and activated mammalian target of rapamycin (mTOR) signaling pathway in the mouse cortex, but lead to a surprising improvement in memory. At this young age, mice also had decreased cerebral Aβ content, which we have not observed at older ages. This was unlikely to be related to altered Aβ synthesis, as both β- and γ-secretase were unchanged. The db mutation also reduced the cortical IL-1β mRNA level and IBA1 protein level in young AD mice, with no significant effect on the activation of microglia and astrocytes. We conclude that the db mutation could transitorily improve the memory of young AD mice, a finding that may be partially explained by the relatively improved glucose homeostasis in the brains of db/AD mice compared to their counterpart AD mice, suggesting that glucose regulation could be a strategy for prevention and treatment of neurodegenerative diseases like AD.

Formaldehyde, Epigenetics, and Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia. The accumulation of β-amyloid plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau protein are two hallmarks of AD. The β-amyloid and tau proteins have been at the center of AD research and drug development for decades. However, most of the clinical trials targeting β-amyloid have failed. Whereas the safety and efficacy of most tau-targeting drugs have not yet been completely assessed, the first tau aggregation inhibitor, LMTX, failed in a late-stage trial, leading to further recognition of the complexities of AD and reconsideration of the amyloid hypothesis and perhaps the tau hypothesis as well. Multilevel complex interactions between genetic, epigenetic, and environmental factors contribute to the occurrence and progression of AD. Formaldehyde (FA) is a widespread environmental organic pollutant. It is also an endogenous metabolite in the human body. Recent studies suggest that elevation of FA in the body by endogenous and/or exogenous exposure may play important roles in AD development. We have demonstrated that FA reduces lysine acetylation of cytosolic histones, thereby compromising chromatin assembly and resulting in the loss of histone content in chromatin, a conserved feature of aging from yeast to humans. Aging is an important factor for AD progression. Therefore, FA-induced inhibition of chromatin assembly and the loss of histones may contribute to AD initiation and/or development. This review will briefly summarize current knowledge on mechanistic insights into AD, focusing on epigenetic alterations and the involvement of FA in AD development. The exploration of chemical exposures as contributing factors to AD may provide new insights into AD mechanisms and could identify potential novel therapeutic targets.

Substâncias administradas para a indução da Doença de Alzheimer em ratos

As estimativas sobre a expansão dos casos da Doença de Alzheimer (DA) no mundo indicam a necessidade de constantes estudos sobre essa patologia ainda sem cura. Os estudos têm investigado a DA em modelos animais não-humanos utilizando substâncias químicas que induzem à DA. O presente estudo teve por objetivo realizar uma revisão da literatura sobre as substâncias usadas em laboratório para reproduzir a DA em ratos. Foram selecionados 44 de 111 estudos analisados, mantendo apenas os artigos que induziram a DA por substâncias químicas. As substâncias identificadas foram o alumínio, a beta-amiloide, a colchicina, a d-galactose, a escopolamina, a estreptozocina e a homocisteína. Verificou-se que dos 44 artigos, a substância mais utilizada foi a beta-amiloide, principal biomarcador da DA. Embora diferentes estudos tenham replicado resultados que simulam a ocorrência de DA em ratos e os tratamentos realizados com ratos em laboratório pareçam promissores, nenhuma cura foi encontrada ainda.

Reader response: Pattern of polyphenol intake and the long-term risk of dementia in older persons.

I read with interest the Lefevre-Arbogast et al.1 article about polyphenyls and reduced incidence of Alzheimer disease (AD). Chronic bacterial infections are associated with development of AD and cause inflammation through activation of innate immunity.2 The increased permeability of the gut and blood–brain barrier induced by microbiota dysbiosis may mediate AD pathogenesis and other neurodegenerative disorders, especially if associated with aging.3 Toll-like receptor 4 is a host defense receptor against invading microorganisms such as bacteria, and is increased in brain tissue associated with amyloid plaque deposition.4 Plant polyphenols have some antibacterial qualities.5 Reducing the amount of gram-negative bacteria from the gastrointestinal tract and oral flora from foods containing polyphenols might reduce AD occurrence though inhibiting bacteria and other organisms such as fungi, which could contribute to development of AD.

Neuroprotective Efficacy of <i>Maytenus emarginata</i> (Wild.) Ding Hou Against Paraquat Induced Oxidative Stress and Neurotoxicity in Drosophila Model System

An investigation has been made to find out the disease altering therapies against a somber ailment called ‘early aging’ which is due to the formation of free radicals during the natural course of metabolism, also act randomly and indiscriminately to damage the cell components. On the contrary, the natural antioxidants in dietetic practice can diminish these free radicals which can perturb further, the progression of these age-related neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) followed by Canine Cognitive dysfunction. As a consequence, a tribal medicinal plant; <i>Maytenus emarginata</i> (Wild.) Ding Hou (family-‘<i>Celastraceae</i>’) was identified which is commonly called ‘Thorny staff tree’ a potent ethno-medicinal plant drug was opted during the interactions held with tribal healers. This candidate plant drug is being practiced as memory-enhancing factor in their tribal medicinal system at Biligirirangana Hills (B. R. Hills) of Chamarajanagara district, India. Hence, the biological screening with Methanol extract of <i>Maytenus emarginata</i> (MEM) was attempted initially for Physico-chemical, Phyto-chemical properties followed by <i>in vitro</i>, <i>in vivo</i> antioxidant and neuroprotective activities using <i>Drosophila melanogaster</i> (Oeragon K) strain adult male flies. In the result, the extract of M exhibited concentration dependent DPPH scavenging activity. The oxidative stress markers employed to access in vivo antioxidant property of M included lipid peroxidation products malondialdehyde (MDA) and hydroperoxide (HP), reduced glutathione (GSH). The modulatory effect of M on superoxide dismutase (SOD) and catalase (CAT) was also determined. The oxidative stress was induced by using paraquat at 15 mM. The concentration of extract for studies was fixed based on LC₅₀ values. There was a significant demolition in the levels of MDA and HP in co-exposure of M with Par treated flies homogenate. The level of SOD and CAT was brought to near basal level in the homogenate of flies co-exposed with M and Par. In negative geotaxis assay it was found that M was able to rescue the flies significantly from deteriorating locomotors dysfunctions. The M extract exhibited significant modulatory activity in regulating oxidative stress markers and antioxidants in the fly homogenate. The extract M also exhibited significant antibacterial property against tested microbial strains. Therefore, the findings point out that, MEM plant drug was found to be most promising in its efficacy which may act as compelling antioxidant agent that can intensify the locomotors functions. Thus, the MEM plant drug therapy can regulate the occurrence of CCD, AD, PD and HD and the normal condition may be reinstalled in the biological system.

Iron Pathophysiology in Alzheimer's Diseases.

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. Increasing evidence suggests that disorders of metal ion metabolism in the brain are one of the risk factors for the pathogenesis of AD. Iron, one of the endogenous metal ions, involves in many important physiological activities in the brain. Iron metabolism mainly depends on iron regulatory proteins including ferritin, transferrin and transferrin receptor, hepcidin, ferroportin, lactoferrin. Abnormal iron metabolism generates hydroxyl radicals through the Fenton reaction, triggers oxidative stress reactions, damages cell lipids, protein and DNA structure and function, leads to cell death, and ultimately influences the process of β-amyloid (Aβ) misfolding and plaque aggregation. Although the results are different, in general, iron has deposition in different brain regions of AD patients, which may impair normal cognitive function and behavior. Therefore, neuroimaging changes have so far been largely attributed to focal iron deposition accompanying the plaques at preclinical stages of AD, and iron-targeted therapeutic strategies have become a new direction. Iron chelators have received a great deal of attention and have obtained good results in scientific experiments and some clinical trials. Future research will also focus on iron as an opportunity to study the mechanism of the occurrence and development of AD from the iron steady state to more fully clarify the etiology and prevention strategies.

Microbes and Alzheimer' disease: lessons from H. pylori and GUT microbiota.

the role of microbes and chronic inflammation in the pathogenesis of Alzheimer' disease (AD) has been postulated by many authors. On the other hand, several studies have reported the main role of H. pylori infection and/or GUT microbiota alteration in promoting chronic inflammation, thus possibly influencing both occurrence and evolution of AD. In this article, we analyze the most important and recent studies performed on this field both on humans and animals and provide possible pathogenic explanations. all main and most recent animal, human, epidemiological and in-silico studies, showed a role of H. pylori and/or dysbiosis in AD, mostly through the promotion of systemic chronic inflammation and/or by triggering molecular mimicry mechanisms. In particular, H. pylori infection seems to be related to a poorer cognitive performance. Indeed, bacteria have been shown to affect neurodegeneration by promoting inflammation, inducing molecular mimicry mechanisms and accumulation of Aβ into the brain. These findings open the way for H. pylori eradicating trials and/or GUT microbiota remodulating strategies. Therefore, further studies are now needed in order to test whether antibiotics, pre and/or probiotics may exert a beneficial effect in the prevention of AD.

RETRACTED: Osthole decreases tau protein phosphorylation via PI3K/AKT/GSK-3β signaling pathway in Alzheimer's disease

Alzheimer's disease (AD), a neurodegenerative disease, was characterized by the loss of memory and progressive cognitive deterioration. Up to now, there has no effective drugs to cure or delay the state of illness. Increasing evidence indicates that hyperphosphorylated tau protein plays a pivotal role in the occurrence and development of AD. Therefore, in present study, we aim to investigate whether osthole (OST) could decrease hyperphosphorylated tau protein in AD and the underlying mechanism. The ability of learning and memory was detected by Morris Water Maze. The pathological changes were detected by H&E staining. The percentage of cells apoptosis was detected by TUNEL assay in vivo and Flow Cytometry in intro. The expressions of tau protein and related proteins in PI3K/Akt/GSK-3β signaling pathway were detected by Western Blot. We found that OST could significantly improve learning and memory dysfunction, ameliorate the histology structure of damaged neural cells in hippocampal area. Moreover, we also found that OST could decrease tau protein phosphorylation as well as inhibit cells apoptosis. To explore the underlying mechanism, we used LY294002 to block PI3K/Akt/GSK-3β signaling pathway, the results from Western bolt showed that the expression of related proteins in PI3K signaling pathway were decreased with LY294002 treated. Taken together, the results indicated that OST could decrease phosphorylated tau levels via activation of PI3K/Akt/GSK-3β signaling pathway. Thus, this study demonstrated that OST might be a potential candidate for the treatment of AD.

PO-123 Voluntary wheel training attenuate brain aging in SAMP8 mice

Objective Alzheimer's disease (AD), is a progressive neurodegenerative disease. The pathological hallmarks including the deposition of senile plaque and neurofibrillary tangles (NFTs) in AD. The underlying molecular mechanisms for AD are not fully understood. Studies have shown that exercise as an economical and popular fitness method, long-term exercise can reduce the risk of AD, delay the occurrence of AD or delay the progression of AD. This study was to investigate the protective effect of the Voluntary wheel on cerebral cortex senescence in SAMP8 mice.&#x0D; Methods Fifteen SPF-class 7-month-old SAMP8 mice were randomly divided into control group (CON), voluntary wheel group (V) and voluntary wheel with chloroquine group (VQ), with 5 mice in each group. Each group was under adaptive feeding for one week. After 3 days of adaptive voluntary wheel training for V and VQ groups, the experiment officially started. The V and VQ groups performed an 8-week voluntary wheel training and the VQ group received a daily intraperitoneal injection of chloroquine (40 mg/kg). After 8 weeks intervention, the Morris water maze test was used to determine the changes in spatial learning and memory ability of each group. After 24 hours of the end of this experiment, the mice were killed by breaking neck. The degree of hippocampal cell injury was detected by Nissl staining; the expression of apoptosis and senescence-associated protein in the cerebral cortex was detected by Western blot.&#x0D; Results Compared with the CON group, the escape latency of the V group mice in the Morris water maze test was significantly shorter (P&lt;0.01), the number of crossing target quadrants was significantly increased (P&lt;0.05), however, the VQ group exacerbate above response compared with CON group. Nissl staining showed that the cells of cerebral cortex in the CON group had obvious damage, while the V group showed significant improvement. The VQ group had a significant damage compared with the V group; Western blot results showed that the expression of AD -like pathological changes such as BACE1 protein in the cortex of group V was significantly decreased, and the expression of P-GSK-3β protein was increased (P&lt;0.01) compared with CON group. On the contrary, compared with V group, VQ alleviated the improvement effect of voluntary running. (P&lt;0.05); the expression of apoptosis-related protein increased, and thedecreased in CON group , while voluntary running intervention down-regulated BAX, Cleaved-caspase3 , increased the Bcl-2 protein level compared with the CON group (P&lt;0.05). Furthermore, compared with the CON group, the expression level of aging-related protein AC-P53 was decreased in the V group, and the expression level of Sirt1 was increased. &#x0D; Conclusions The 8-week voluntary wheel training can significantly improve the learning and memory ability of SAMP8. Mechanismly, voluntary wheel training can improve the senescence of cerebral cortex by inhibiting cell apoptosis, the expression of AD –like pathological protein and increasing Sirt1 protein level.

Incidence of dementia in patients with adult-onset epilepsy of unknown causes

Epilepsy is generally considered to occur most commonly in childhood; however, several epidemiological studies confirmed that its occurrence increases from middle age [ [1] Hauser W.A. Seizure disorders: the changes with age. Epilepsia. 1992; 33: S6-S14 Crossref PubMed Scopus (344) Google Scholar , [2] Olafsson E. Ludvigsson P. Gudmundsson G. Hesdorffer D. Kjartansson O. Hauser W.A. Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study. Lancet Neurol. 2005; 4: 627-634 Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar ], and is the third most common neurological disease affecting the elderly, following dementia and cerebrovascular disease (CVD) [ [3] Brodie M.J. Kwan P. Epilepsy in elderly people. BMJ. 2005; 331: 1317-1322 Crossref PubMed Scopus (141) Google Scholar , [4] Werhahn K.J. Epilepsy in the elderly. Dtsch Arztebl Int. 2009; 106: 135-142 PubMed Google Scholar ]. These diseases interact with each other in later life. The leading etiology of elderly-onset epilepsy is CVD [ [5] Hauser W.A. Rowan A.J. Ramsay R.E. Epidemiology of Seizures and Epilepsy in the Elderly. Butterworth-Heinemann, Boston1997: 7-18 Google Scholar , [6] Wallace H. Shorvon S. Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922, and age-specific fertility rates of women with epilepsy. Lancet. 1998; 352: 1970-1973 Abstract Full Text Full Text PDF PubMed Scopus (322) Google Scholar ], and CVD is a major risk factor for dementia with neurodegenerative disease, especially Alzheimer's disease (AD) [ [7] Petrovitch H. Ross G.W. Steinhorn S.C. Abott R.D. Markesbery W. Davis D. et al. AD lesions and infarcts in demented and non-demented Japanese-American men. Ann. Neurol. 2005; 57: 98-103 Crossref PubMed Scopus (202) Google Scholar , [8] J. Obrien R. Vascular dementia: atherosclerosis, cognition and Alzheimer's disease. Curr. Alzheimer Res. 2011; 8: 341-344 Crossref PubMed Scopus (13) Google Scholar ]. Adult-onset epilepsy is considered as a consequence of structural damage of the central nervous system (CNS), and the existence of AD, a typical neurodegenerative disease, also increases the occurrence of epilepsy [ [9] Scarmeas N. Honig L.S. Choi H. Cantero J. Brandt J. Blacker D. et al. Seizures in Alzheimer disease: who, when, and how common?. Arch. Neurol. 2009; 66: 992-997 Crossref PubMed Scopus (221) Google Scholar ]. This clinical finding is supported by several basic studies using a transgenic mouse model of AD, which demonstrated that deposited amyloid-β (Aβ) causes epileptiform discharges in the cortex, nonconvulsive seizures, and cognitive dysfunction [ [10] Palop J.J. Chin J. Roberson E.D. Wang J. Thwin M.T. Bien-Ly N. et al. Compensatory remodering of inhibitory hippocampal circuits in mouse models in Alzheimer's disease. Neuron. 2007; 55: 697-711 Abstract Full Text Full Text PDF PubMed Scopus (1121) Google Scholar , [11] Huang Y. Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012; 148: 1204-1222 Abstract Full Text Full Text PDF PubMed Scopus (1358) Google Scholar ]. Taking into account the evidence that Aβ deposition starts >10 years before clinical signs of AD appear [ [12] Villemagne V.L. Burnham S. Bourgeat P. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013; 12: 357-367 Abstract Full Text Full Text PDF PubMed Scopus (1410) Google Scholar ], epilepsy may develop earlier than AD. To test this hypothesis, we retrospectively studied the occurrence of AD in patients with adult-onset epilepsy of unknown causes to elucidate whether these patients are more likely to develop AD than control patients. Moreover, to determine whether an atherosclerotic factor affects the occurrence of AD, we also investigated the occurrence of CVD in both groups.

Recognition of Alzheimer’s Disease Related miRNAs Based on Genome-Wide Association Study Data

To analyze the mi RNA expression profile of patients with Alzheimer's disease (AD) in order to intensively study the relationship between mi RNA and the occurrence and development of AD, and to lay the foundations for the finding of new molecular markers. Use mi RNA chip to detect the mi RNA expression profiles of cerebrospinal fluid in AD patients and elderly people with normal cognition, and perform preliminary bioinformatics analysis. Real-time PCR was used to verify the results of mi RNA chip detection. The results of mi RNA chip analysis showed that there were many differentially expressed mi RNA in cerebrospinal fluid of AD patients and elderly people with normal cognition. Cerebrospinal fluid in AD patients has a specific mi RNA expression profile, suggesting that a new molecular marker for AD may be found in the expression of mi RNA.

Classifying Alzheimer's disease with brain imaging and genetic data using a neural network framework.

A long-standing question is how to best use brain morphometric and genetic data to distinguish Alzheimer's disease (AD) patients from cognitively normal (CN) subjects and to predict those who will progress from mild cognitive impairment (MCI) to AD. Here, we use a neural network (NN) framework on both magnetic resonance imaging-derived quantitative structural brain measures and genetic data to address this question. We tested the effectiveness of NN models in classifying and predicting AD. We further performed a novel analysis of the NN model to gain insight into the most predictive imaging and genetics features and to identify possible interactions between features that affect AD risk. Data were obtained from the AD Neuroimaging Initiative cohort and included baseline structural MRI data and single nucleotide polymorphism (SNP) data for 138 AD patients, 225 CN subjects, and 358 MCI patients. We found that NN models with both brain and SNP features as predictors perform significantly better than models with either alone in classifying AD and CN subjects, with an area under the receiver operating characteristic curve (AUC) of 0.992, and in predicting the progression from MCI to AD (AUC=0.835). The most important predictors in the NN model were the left middle temporal gyrus volume, the left hippocampus volume, the right entorhinal cortex volume, and the APOE (a gene that encodes apolipoprotein E) ɛ4 risk allele. Furthermore, we identified interactions between the right parahippocampal gyrus and the right lateral occipital gyrus, the right banks of the superior temporal sulcus and the left posterior cingulate, and SNP rs10838725 and the left lateral occipital gyrus. Our work shows the ability of NN models to not only classify and predict AD occurrence but also to identify important AD risk factors and interactions among them.

MicroRNA-125b promotes neurons cell apoptosis and Tau phosphorylation in Alzheimer's disease.

Alzheimer's disease (AD) is considered as one of the most common neural degenerative diseases in human. Although the continuous investigations about AD have been made in recent decades, the pathogenesis of this disease is still not definitely confirmed. MicroRNA-125b (miR-125b) is extensive expressed in many types of human tissues and played pivotal regulatory roles in diverse biological process. In the present study, we aimed to explore the roles of miR-125b in regulating neurons cell apoptosis under AD condition. The possible molecular mechanisms were also investigated. We found that miR-125b was up-regulated in patients with AD. Transfection with miR-125b significantly enhanced the apoptosis of neurons cells and phosphorylation of Tau by activation of cyclin-dependent kinase 5 (CDK5) and p35/25. Forkhead box Q1 (FOXQ1) was the direct target gene of miR-125b, which involved in the effects of miR-125b on neurons cell apoptosis and phosphorylation of Tau. Our research interpreted the mechanism of up-regulation of miR-125b in pathological Tau phosphorylation and AD occurrence. miR-125b may be a novel regulator of AD progress and could be as a therapeutic target for AD therapy.

Alzheimer's disease and cytokine IL-10 gene polymorphisms: is there an association?

Alzheimer's disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.

Expression of microRNA‑222 in serum of patients with Alzheimer's disease.

The aim of the present study was to determine the association between Alzheimer's disease (AD) and microRNA‑222 in the serum of patients with AD. The expression of microRNAs was detected and the results were verified using microarray analysis and reverse transcription‑quantitative polymerase chain reaction. The results indicated that there were 35 strips of microRNA in the mild AD group, in which the difference of expression signal was >500IU/ml. There were 26 strips of microRNA with a difference in expression signal of >500IU/ml in the mild and moderate AD groups. The downregulation of microRNA‑222 in the mild and moderate groups was statistically significant (P<0.01), and the expression of microRNA‑222 in the moderate group was significantly lower, compared with that in the mild AD group (P<0.05). It was concluded that microRNA‑222 may affect the occurrence and development of AD through a variety of mechanisms, and may serve as a biomarker for the early diagnosis of AD.

Dynamical differential networks and modules inferring disrupted genes associated with the progression of Alzheimer's disease.

In order to understand the pathogenic factors that initiate the processes of Alzheimer's disease (AD), a method of inference of multiple differential modules (iMDM) to conduct analysis was performed on the gene expression profile of AD. A total of 11,089 genes and 588,391 interactions were gained based on the gene expression profile and protein-protein interaction network. Subsequently, three differential co-expression networks (DCNs) were constructed with the same nodes but different interactions, and eight multiple differential modules (M-DMs) were identified. Furthermore, by performing Module Connectivity Dynamic Score to quantify the change in the connectivity of component modules, two M-DMs were identified: Module 1 (P=0.0419) and 2 (P=0.0419; adjusted, P≤0.05). Finally, hub genes of MDH1, NDUFAB1, NDUFB5, DDX1 and MRPS35 were gained via topological analysis conducted on the 2 M-DMs. In conclusion, the method of iMDM was suitable for conducting analysis on AD. By applying iMDM, 2 M-DMs were successfully identified and the MDH1, NDUFAB1, NDUFB5, DDX1 and MRPS35 genes were predicted to be important during the occurrence and development of AD.

MICRORNA AND GENE NETWORKS UNDERLYING THE INVERSE ASSOCIATION OF CANCER AND ALZHEIMER’S DISEASE

An inverse association of cancer and Alzheimer's disease (AD) has been reported by epidemiological studies but the underlying biological mechanisms remain unclear. Data from the Religious Orders Study/Memory and Aging Project (ROS/MAP) included 1448 individuals with age of death, cancer history (CA+/-), and clinical diagnosis proximate to death (no cognitive impairment (NCI, n=472), mild cognitive impairment (MCI, n=379), and AD dementia (n=597)). 1237 had data for brain neurofibrillary tangles (NFTs) and neuritic plaques (NPs). The inverse relationship of cancer and AD was tested using chi-square and survival analyses. The interaction of clinical diagnosis and cancer history with neuropathology was tested using ANCOVA. Additional data included brain expression for microRNAs (n=667) and genes (n=476). Weighted gene co-expression network analysis was performed on microRNAs and genes. Networks were tested for correlation with clinical diagnosis, cancer history, and NFTs. Gene ontology (GO) Reactome pathway enrichment was performed on significant modules. Cancer history was inversely associated with clinical diagnosis (p<0.001), with more CA+ in NCI (49%) compared to MCI (43%) and AD dementia (34%) (Figure 1A). Those with CA+ AD dementia showed later age of onset (Figure 1B; p<0.001). Although cancer history was not associated with NPs (p=0.588), AD dementia CA+ had fewer NFTs (p=0.024; Figure 1C) (Yarchoan et al., 2016), providing a potential biological link between cancer history and reduced AD dementia risk. One microRNA module correlated negatively with cancer history (p=0.02) and positively with clinical diagnosis (p=0.01) (Figure 2). Five gene modules correlated with clinical diagnosis and cancer history (Figure 2). The most significantly enriched pathway was ‘metallothioneins bind metals’ (p=2.06x10-18), within module Gene_M1. Gene_M1 correlated with clinical diagnosis, cancer history, and NFTs, and included 10/30 metallothionein genes. The hub microRNA from the significant microRNA module targets the Gene_M1 hub gene metallothionein 1A, suggesting an association between these network modules and the occurrence of cancer and AD.

Altered protein glycosylation predicts Alzheimer's disease and modulates its pathology in disease model Drosophila

The pathological hallmarks of Alzheimer's disease (AD) are pathogenic oligomers and fibrils of misfolded amyloidogenic proteins (e.g., β-amyloid and hyper-phosphorylated tau in AD), which cause progressive loss of neurons in the brain and nervous system. Although deviations from normal protein glycosylation have been documented in AD, their role in disease pathology has been barely explored. Here our analysis of available expression data sets indicates that many glycosylation-related genes are differentially expressed in brains of AD patients compared with healthy controls. The robust differences found enabled us to predict the occurrence of AD with remarkable accuracy in a test cohort and identify a set of key genes whose expression determines this classification. We then studied in vivo the effect of reducing expression of homologs of 6 of these genes in transgenic Drosophila overexpressing human tau, a well-established invertebrate AD model. These experiments have led to the identification of glycosylation genes that may augment or ameliorate tauopathy phenotypes. Our results indicate that OstDelta, l(2)not and beta4GalT7 are tauopathy suppressors, whereas pgnat5 and CG33303 are enhancers, of tauopathy. These results suggest that specific alterations in protein glycosylation may play a causal role in AD etiology.