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NRG3 Gene Is Associated With the Risk and Age at Onset of Alzheimer DiseaseWang, Ke Sheng, Xu, Nuo, Wang, Liang, Aragon, Lorenzo, Ciubuc, Radu, Arana, Tania Bedard, Mao, Chunxiang, Petty, Leonora, Briones, David, Su, Brenda Bin, Luo, Xingguang, Camarillo, Cynthia, Escamilla, Michael A., Xu, Chun 01 February 2014 (has links)
The Neuregulin 3 (NRG3) gene at 10q22-q24 has been implicated in multiple psychiatric traits such as cognitive impairment. We therefore hypothesized that NRG3 gene polymorphisms may play a role in Alzheimer disease (AD). This present study explored the association of NRG3 with the age at onset (AAO) of AD and the risk of developing AD. Secondary data analysis of 257 single-nucleotide polymorphisms (SNPs) in NRG3 gene was performed in 806 Alzheimer's disease patients and 782 controls using logistic regression and linear regression analyses. Eight SNPs were associated with the risk of AD (p < 0.05), while linear regression analysis showed 33 SNPs associated with the AAO of AD (p < 0.05). Two-SNP haplotype analyses based on UNPHASED revealed that the G-C haplotype from rs17685233 and rs17101017 was significantly associated with AD (p = 0.0031) and the A-G haplotype from rs504522 and rs474018 as well as the A-G haplotype from rs504522 and rs2483295 were more significantly associated with the AAO of AD (p = 6.72 × 10-5). Using an independent family-based sample, we found one SNP rs11192423 associated with AAO both in the case-control sample (p = 0.0155) and in the family sample (p = 0.0166). In addition, we observed nominally significant associations with AD and AAO for several flanking SNPs (p < 0.05). This is the first study demonstrating that genetic variants in the NRG3 gene play a role in AD. Our results also revealed that SNPs in the NRG3 genes were more strongly associated with AAO of AD.
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Postmenopausal Estrogen Therapy and Alzheimer Disease: Overall Negative FindingsRoberts, Rosebud, Cha, Ruth H., Knopman, David S., Petersen, Ronald C., Rocca, Walter A. 01 July 2006 (has links)
An inverse association between estrogen therapy (ET) and Alzheimer disease (AD) has been reported in some, but not in all studies. We investigated the association between ET and AD in postmenopausal women using a population-based case-control design. Women who developed AD from 1985 through 1989 in Rochester, MN (cases, n=264) were individually matched by age (±1 y) to control women free of dementia from the same population (controls, n=264). ET exposure (≥6 mo after menopause) was ascertained by abstracting the complete medical records archived in the records-linkage system of the Rochester Epidemiology Project. The frequency of ET use was similar in cases (11.4%) and controls [10.6%; odds ratio=1.10; 95% confidence interval (CI)=0.63-1.93]. However, cases who used ET had a suggestive trend for an earlier age at start of ET compared with controls (median, 49.0 vs. 50.5 y; P=0.06). Although smoking (ever vs. never) was not associated with AD overall, we observed an interaction between smoking and ET. The odds ratio of AD in ET users was 4.55 (95% CI=1.33-15.53) among smokers, but was 0.68 (95% CI=0.35-1.32) among never-smokers (P for interaction=0.01). Our findings do not confirm a significant association between ET and AD overall; however, the possible interaction with smoking deserves further study.
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Gene-Environment Interplay in Neurogenesis and NeurodegenerationPalomo, Tomás, Archer, Trevor, Beninger, Richard J., Kostrzewa, Richard M. 01 December 2004 (has links)
Factors associated with predisposition and vulnerability to neurodegenerative disorders may be described usefully within the context of gene-environment interplay. There are many identified genetic determinants for so-called genetic disorders, and it is possible to duplicate many elements of recognized human neurodegenerative disorders in either knock-in or knock-out mice. However, there are similarly, many identifiable environmental influences on outcomes of the genetic defects; and the course of a progressive neurodegenerative disorder can be greatly modified by environmental elements. Constituent cellular defense mechanisms responsive to the challenge of increased reactive oxygen species represent only one crossroad whereby environment can influence genetic predisposition. In this paper we highlight some of the major neurodegenerative disorders and discuss possible links of gene-environment interplay. The process of adult neurogenesis in brain is also presented as an additional element that influences gene-environment interplay. And the so-called priming processes (i.e., production of receptor supersensitization by repeated drug dosing), is introduced as yet another process that influences how genes and environment ultimately and co-dependently govern behavioral ontogeny and outcome. In studies attributing the influence of genetic alteration on behavioral phenotypy, it is essential to carefully control environmental influences.
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Analysis of Ptprk Polymorphisms in Association With Risk and Age at Onset of Alzheimer's Disease, Cancer Risk, and CholesterolChen, Yang, Xu, Chun, Harirforoosh, Sam, Luo, Xingguang, Wang, Ke Sheng 01 January 2018 (has links)
The human receptor-type protein-tyrosine phosphatase kappa (PTPRK) gene is highly expressed in human brain and was previously associated with an increased risk of neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in PTPRK with the risk and age at onset (AAO) of Alzheimer's disease (AD) in 791 AD patients and 782 controls. Our data analysis showed that five SNPs (top SNP rs4895829 with p = 0.0125) were associated with the risk of AD based on a multiple logistic regression (p < 0.05); while six SNPs (top SNP rs1891150 with p = 8.02 × 10−6) were associated with AAO by using a multiple linear regression analysis. Interestingly, rs2326681 was associated with both the risk and AAO of AD (p = 4.65 × 10−2 and 5.18 × 10−3, respectively). In a replication study, the results from family-based association test - generalized estimating equation (GEE) statistics and Wilcoxon test showed that seven SNPs were associated with the risk of AD (top SNP rs11756545 with p = 1.02 × 10−2) and 12 SNPs were associated with the AAO (top SNP rs11966128 with p = 1.39 × 10−4), respectively. One additional sample showed that four SNPs were associated with risk of cancer (top SNP rs1339197 with p = 4.1 × 10−3), 12 SNPs associated with LDL-cholesterol (top SNP rs4544930 with p = 3.47 × 10−3), and eight SNPs associated with total cholesterol (top SNP rs1012049 with p = 6.09 × 10−3). In addition, the AD associated rs4895829 was associated with the gene expression level in the cerebellum (p = 7.3 × 10−5). The present study is the first study providing evidence of several genetic variants within the PTPRK gene associated with the risk and AAO of AD, risk of cancer, LDL and total cholesterol levels.
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Att vara närstående till en person med alzheimers sjukdom : en litteraturöversikt / Being a relative to a person with alzheimer’s disease : a literature reviewAbdirashid, Samsam, Mohamed, Hawo January 2022 (has links)
Bakgrund: Alzheimers sjukdom är en neurodegenerativ sjukdom som drabbar individen med sakta smygande symtom och påverkar det kognitiva, framförallt minnet. Diagnosen gör att personen ofta inte kan klara av vardagen, vilket innebär ett stort ansvar för närstående. Sjuksköterskans uppgift är att ge stöd till både anhöriga och närstående. Syfte: Att beskriva närståendes upplevelser av att vårda en anhörig med Alzheimers sjukdom. Metod: Metoden var en kvalitativ litteraturöversikt som är baserad på nio vetenskapliga artiklar som är hämtade från PubMed och Cinahl Complete. Resultat: Analysen resulterades i fyra huvudfynd: Närstående erfarenheter av att ta hand om den sjuke, vilket visade att en del saknade erfarenheter och att det var en stor påfrestning att ta hand om den sjuke. Svårigheter att kunna balansera sin vardag, vilket visade att närstående hade svårt att balansera mellan det sociala livet och livet i hemmet. Bristande kunskap, vilket visade stor brist på kunskap att ta hand om den anhörige. Brist på egen tid och återhämtning, vilket visade att närstående inte fick tid för återhämtning vilket gav negativa effekter på närståendes hälsa. Sammanfattning: Närstående som vårdar en person med Alzheimers sjukdom drabbas av både psykisk och fysisk belastning. Ett multiprofessionellt team som kan stödja och öka kunskapen hos närstående kan minska negativa upplevelser och ge trygghet i vårdandet. / Background: Alzheimer is a disease that affects cognitively. People with Alzheimer's have difficulties with communication, taking in information and their daily routines. This in turn, leads to the person needing support in their daily life. Aim: The aim was to describe loved one's experiences of caring for a relative with Alzheimer's disease. Method: This was a qualitative literature review based on nine scientific articles retrieved from the databases PubMed and Cinahl Complete. Results: The analysis resulted in four themes: Experiences of care-taking of the sick one showing that relatives do not have experiences which caused stress. Difficulties to balance their daily life, showing that relatives found it difficult to balance between their social life and the care for their loved one. Lack of knowledge resulting in difficulties in caring for their loved one. Lack of own time and recovery resulting in no time to recover, which in turn caused negative health effects. Others, on the other hand, described a sense of purpose in caring for the relative. Summary: Individuals who care for a relative with Alzheimer’s disease have strong feelings and need a lot of support from different professions and society. Knowledge, communication and trust can create a better quality of life for relatives caring for a loved one.
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Sex differences in stress responsivity, glucocorticoid signaling, and diseaseNguyen, Elizabeth T. 14 October 2019 (has links)
No description available.
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Increased Prevalence in Alzheimer Disease in the Northeast Tennessee Region of the United StatesOrimaye, Sylvester O., Southerland, Jodi L., Oke, Adekunle O., Ajibade, Aderonke 01 July 2020 (has links)
This study describes the changes in prevalence odds ratios (PORs) for Alzheimer disease (AD) in the northeast Tennessee region (NTR) during a 3-year period, describes the statistical assessment process, and critically assesses the database from which the statistical association was derived. The article also examines several beliefs pertinent to the clinical management of AD in the NTR from the perspective of professionals delivering services. Methods We extracted prevalence data for NTR counties for 2013, 2014, and 2015 from the Centers for Medicare and Medicaid Services Geographic Variation Public Use File. We used the crude prevalence and the 2010 US Census Data fixed population for each county to compute the POR. The 2013 Economic Research Service Rural-Urban Continuum Codes were used to identify rural and urban counties in the NTR. We collected primary data on the perceived observation of the increasing prevalence in the NTR during the last 3 years and barriers to early diagnosis through an online survey from 44 experts and professionals working in AD-related fields within the NTR. Results The PORs of AD in rural counties in NTR increased by 18.3%, 4.7%, and 19% compared with urban counties for 2013, 2014, and 2015, respectively. The POR of AD for the entire NTR region increased by 22.7%, 22.5%, and 21.2% compared with other regions in Tennessee for 2013, 2014, and 2015, respectively. Compared with 2012, 68.4% of respondents currently work with more individuals with AD; 71.8% reported that the NTR has a higher number of late-stage diagnoses of AD. A total of 92.3% strongly agreed that early detection of AD is important, and 95% agreed that early diagnosis could prolong the lives of patients with AD; 51.2% were unaware of existing AD screening services. Reported barriers were denial, lack of patient awareness, inefficient screening methods, communication, and lack of community resources. Conclusions Increased prevalence of AD among inhabitants in the NTR and identified barriers to early screening or diagnosis in the management of AD were identified. Access to early screening techniques must be prioritized in deprived areas within the NTR. Healthcare providers and medical professionals in the NTR must be well equipped with the required training and resources to respond adequately to the increasing prevalence of AD.
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[en] DESIGN AND ALZHEIMER S DISEASE: GUIDING CONCEPTS AND GUIDELINES FOR ADAPTING THE ELDERLY WITH DEMENTIA S HOME / [pt] DESIGN E DOENÇA DE ALZHEIMER: CONCEITOS NORTEADORES E DIRETRIZES PARA A ADAPTAÇÃO DO LAR DO IDOSO COM DEMÊNCIAMARIA CAROLINA DIAS DE AZEVEDO 17 June 2021 (has links)
[pt] O aumento na expectativa de vida elevou o número de idosos com Doença de Alzheimer (DA), que atinge uma pessoa a cada sete segundos. No Brasil, estima-se que haja um milhão de idosos com a doença, uma demência que afeta sua interação com as pessoas e com o lugar em que vivem. Projetos para a habitação de idosos com demência visam sua segurança, mais do que demandas de ordem subjetiva. Esta é uma investigação sobre meios tangíveis de contribuir com aspectos intangíveis da vida de idosos com DA. Para tanto, realizou-se busca sistematizada de adaptações feitas no ambiente arquitetônico em que habitam pessoas com demência, abrangendo artigos de periódicos indexados na base de dados MEDline e consulta a outras fontes. Foram organizados, em paralelo, conceitos sobre espaço, lugar, casa e lar, identificando-se estreita relação entre a noção de lar e o sentimento de pertencimento. Foram levantados, também, dados sobre a DA, com atenção especial para os efeitos relacionados à interação do idoso com seu lar em particular. Destacaram-se as intervenções destinadas à orientação espaço-temporal, por abarcarem conceitos de estimulação sensorial e considerarem a importância de um lugar de aspecto familiar, seguro, que favorece a autonomia, a independência, a interação social e a privacidade, atributos fundamentais para o projeto de ambientes para idosos com demência. Concluiu-se que o projeto de ambientes mais compreensíveis pode contribuir com a qualidade de vida dos idosos com DA. / [en] The rise in life expectancy increased the number of elderly people with AD, which affects one person every seven seconds. In Brazil, it is estimated that there are one million elderly people with Alzheimer s Disease (AD), dementia that affects their interaction with people and the place where they live. Projects for the housing of elderly people with dementia aim at their safety, rather than subjective demands. This is an investigation of tangible ways to contribute to intangible aspects of the lives of elderly people with AD. To this end, a systematic search for adaptations was made in the architectural environment in which people with dementia live, covering articles from periodicals indexed in the MEDline database and consultation with other sources. Concepts about space, place, house and home were organized in parallel, identifying a close relationship between the notion of home and the feeling of belonging. Data on AD were also collected, with special attention to the effects related to the interaction of the elderly with their home, in particular. The interventions aimed at time-spatial orientation stood out, as they encompass concepts of sensory stimulation and considering the importance of a family-friendly, safe place that favors autonomy, independence, social interaction and privacy, fundamental attributes for the design of environments for elderly people with dementia. It was concluded that the design of more understandable environments can contribute to the quality of life of the elderly with AD.
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Elucidate environmental impact on the establishment of a persistent neurotoxic state via novel engineering toolsHan Zhao (17131642) 11 October 2023 (has links)
<p dir="ltr">Neurodegenerative disease (ND) is a debilitating neurological disorder characterized by progressive loss of neurons in central nervous system (CNS), resulting in the decline in memory, cognition and motor functions. Alzheimer's disease (AD) and Parkinson's disease (PD) are the two of the most prevalent NDs, affecting millions of individuals in the United States. While hundreds of genetic risk factors have been identified in association with ND, familial cases with genetic origin only account for 10% and 15% of diagnosed AD and PD incidences, respectively. The majority of ND cases occur sporadically. Mounting evidence from epidemiology studies suggests that environmental stressors are one of the key ND associated risk factors where exposure to environmental stressors leads to the on-set of ND years or decades later. Little is known about the molecular mechanism facilitating the establishment of the persistent and potentially permanent neurotoxic state after exposures, particularly at a developmental stage. Hence, there is a pressing need in understanding the cellular machineries involved in establishment of a persistent neurotoxic state resulting from early-life exposure to environmental toxins. Subcellular compartments are crucial for the maintenance of neuronal homeostasis. Alterations in various subcellular compartments, including the nucleus, mitochondria, and lysosomes, have been commonly noted in cases of AD and PD; and are believed to play a crucial role in the establishment of a persistent neurotoxic state. The primary goal of my thesis is thus to uncover the dysregulation in multiple subcellular compartments and their contributes to ND pathogenesis induced by early-in-life exposure to environmental stressors, including atrazine (ATZ), per-and polyfluoroalkyl substances (PFAS), and neurofibrillary tangles.</p><p dir="ltr">I started by developing live-cell compatible tools to track cellular and sub-cellular changes. Mitochondria DNA methylation is of particular interest, due to its potential regulatory role in the expression of electron transport chain (ETC) subunits and thus mitochondrial activity. Thus, I started expanding the mitochondria probe tool set by designing a novel probe targeting methylated CpGs of mitochondrial DNA (mtDNA). We demonstrated the capability of our probe to reveal spatial distribution of methylated mtDNA and capture mtDNA methylation change at single cell level. Combined with our previously developed probe for nuclear DNA methylation, we monitored mtDNA and nuclear DNA methylation simultaneously on the single-cell level where unsynchronized dynamics of DNA methylation from nucleus and mitochondria were discovered.</p><p dir="ltr">Our tool offers a unique opportunity to understand epigenetic regulation of mtDNA and its dynamic response to microenvironment and cellular changes. Later, I further extended these efforts to develop in situ probes for tracking the formation of tau aggregates based on fluorescence resonance energy transfer (FRET); and demonstrated the superior performance of our engineered probes compared to the current state-of-the-art.</p><p dir="ltr">I explored two neuronal culture systems, namely SH-SY5Y- and human induced pluripotent stem cell (hiPSC)-derived neurons; and their feasibility in studying neurotoxic effects of developmental exposure to environmental stressors. Specifically, I used SH-SY5Y derived neuron-like cells to study the impact of pre-differentiation exposure to PFOA, abundant chemical in environment due to its historical uses in consumer products and industrial applications. hiPSC-derived neurons were used to study the effects of developmental exposure to ATZ. Both studies identified cellular changes, for example neurite morphology and expression of enzyme catalyzing the production of neurotransmitters, that last after completion of differentiation. We also identified changes of pathogenic markers aligning with increased PD risks associated with developmental PFOA and ATZ exposure. Compared to SH-SY5Y, hiPSC-derived neurons were more advantageous due to their ability to recapitulate neuronal activity and pathogenic changes related to ND, and thus were used in my follow-up studies.</p><p dir="ltr">I adopted hiPSC derived neuron model to study the molecular mechanism of ND using established ND etiology. Patients with neurodegenerative disorders (ND) exhibit varying levels and temporal patterns of aggregated β-amyloid (Aβ) and tau protein. We exposed neurons derived from hiPSC with preformed fibrils (PFFs) of Aβ, tau and Aβ+tau, respectively. These treatments result in significant alterations in neurite network morphology, nuclear morphology, chromatin compactness and synaptic density. Interestingly, Aβ and tau fibrils seem to have opposite effects on mitochondrial membrane potential on neurites. Increased quantity of lysosomes was found in neurons treated with Aβ, tau and Aβ+tau, while decrease of lysosomal acidity was only observed in neurons treated with Aβ and tau sequentially. Collectively, our data suggests the potential synergy between Aβ and tau in establishing a neurotoxic state.</p><p dir="ltr">In summary, my thesis work has developed enabling engineering tools to monitor cellular and subcellular changes in neurons; identified hiPSC-derived neurons as a promising platform for studying developmental neurotoxicity; and paved the way towards understanding multi-etiology and its molecular underpinning for ND.</p>
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PHOSPHORYLATION AND SEQUENCE DEPENDENCY OF NEUROFILAMENT PROTEIN OXIDATIVE MODIFICATION IN ALZHEIMER DISEASELiu, Quan January 2005 (has links)
No description available.
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