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  1. Article ; Online: Alterations in erythrocyte fatty acid composition in preclinical Alzheimer’s disease

    Kathryn Goozee / Pratishtha Chatterjee / Ian James / Kaikai Shen / Hamid R. Sohrabi / Prita R. Asih / Preeti Dave / Bethany Ball / Candice ManYan / Kevin Taddei / Roger Chung / Manohar L. Garg / Ralph N. Martins

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 9

    Abstract: Abstract Brain and blood fatty acids (FA) are altered in Alzheimer’s disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study ... ...

    Abstract Abstract Brain and blood fatty acids (FA) are altered in Alzheimer’s disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65–90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand 18F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio; SUVR < 1.35, N = 65) and high NAL or preclinical AD (SUVR ≥ 1.35, N = 35) wherein, linear models were employed to compare FA compositions between the two groups. Increased arachidonic acid (AA, p < 0.05) and decreased docosapentaenoic acid (DPA, p < 0.05) were observed in high NAL. To differentiate low from high NAL, the area under the curve (AUC) generated from a ‘base model’ comprising age, gender, APOEε4 and education (AUC = 0.794) was outperformed by base model + AA:DPA (AUC = 0.836). Our findings suggest that specific alterations in erythrocyte FA composition occur very early in the disease pathogenic trajectory, prior to cognitive impairment. As erythrocyte FA levels are reflective of tissue FA, these alterations may provide insight into the pathogenic mechanism(s) of the disease and may highlight potential early diagnostic markers and therapeutic targets.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Alterations in serum kynurenine pathway metabolites in individuals with high neocortical amyloid-β load

    Pratishtha Chatterjee / Kathryn Goozee / Chai K. Lim / Ian James / Kaikai Shen / Kelly R. Jacobs / Hamid R. Sohrabi / Tejal Shah / Prita R. Asih / Preeti Dave / Candice ManYan / Kevin Taddei / David B. Lovejoy / Roger Chung / Gilles J. Guillemin / Ralph N. Martins

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    A pilot study

    2018  Volume 10

    Abstract: Abstract The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer’s disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive ... ...

    Abstract Abstract The kynurenine pathway (KP) is dysregulated in neuroinflammatory diseases including Alzheimer’s disease (AD), however has not been investigated in preclinical AD characterized by high neocortical amyloid-β load (NAL), prior to cognitive impairment. Serum KP metabolites were measured in the cognitively normal KARVIAH cohort. Participants, aged 65–90 y, were categorised into NAL+ (n = 35) and NAL− (n = 65) using a standard uptake value ratio cut-off = 1.35. Employing linear models adjusting for age and APOEε4, higher kynurenine and anthranilic acid (AA) in NAL+ versus NAL− participants were observed in females (kynurenine, p = 0.004; AA, p = 0.001) but not males (NALxGender, p = 0.001, 0.038, respectively). To evaluate the predictive potential of kynurenine or/and AA for NAL+ in females, logistic regressions with NAL+/− as outcome were carried out. After age and APOEε4 adjustment, kynurenine and AA were individually and jointly significant predictors (p = 0.007, 0.005, 0.0004, respectively). Areas under the receiver operating characteristic curves were 0.794 using age and APOEε4 as predictors, and 0.844, 0.866 and 0.871 when kynurenine, AA and both were added. Findings from the current study exhibit increased KP activation in NAL+ females and highlight the predictive potential of KP metabolites, AA and kynurenine, for NAL+. Additionally, the current study also provides insight into he influence of gender in AD pathogenesis.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree

    Pratishtha Chatterjee / Michelle Tegg / Steve Pedrini / Anne M. Fagan / Chengjie Xiong / Abhay K. Singh / Kevin Taddei / Samantha Gardener / Colin L. Masters / Peter R. Schofield / Gerhard Multhaup / Tammie L. S. Benzinger / John C. Morris / Randall J. Bateman / Steven M. Greenberg / Mark A. van Buchem / Erik Stoops / Hugo Vanderstichele / Charlotte E. Teunissen /
    Graeme J. Hankey / Marieke J. H. Wermer / Hamid R. Sohrabi / Ralph N. Martins / the Dominantly Inherited Alzheimer Network

    International Journal of Molecular Sciences, Vol 22, Iss 2931, p

    A Cross-Sectional and Longitudinal Investigation

    2021  Volume 2931

    Abstract: Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study ... ...

    Abstract Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8;MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001; Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001; Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform ( p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform ( p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required.
    Keywords amyloid-beta ; plasma amyloid-beta ; blood biomarkers ; cerebral amyloid angiopathy ; early diagnosis ; hereditary cerebral haemorrhage with amyloidosis—Dutch type ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

    Gemma Cadby / Corey Giles / Phillip E. Melton / Kevin Huynh / Natalie A. Mellett / Thy Duong / Anh Nguyen / Michelle Cinel / Alex Smith / Gavriel Olshansky / Tingting Wang / Marta Brozynska / Mike Inouye / Nina S. McCarthy / Amir Ariff / Joseph Hung / Jennie Hui / John Beilby / Marie-Pierre Dubé /
    Gerald F. Watts / Sonia Shah / Naomi R. Wray / Wei Ling Florence Lim / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Tenielle Porter / Michael Vacher / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Kevin Taddei / Matthias Arnold / Gabi Kastenmüller / Kwangsik Nho / Andrew J. Saykin / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / John Blangero / Peter J. Meikle / Eric K. Moses

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 17

    Abstract: Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD. ...

    Abstract Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.
    Keywords Science ; Q
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

    Kevin Huynh / Wei Ling Florence Lim / Corey Giles / Kaushala S. Jayawardana / Agus Salim / Natalie A. Mellett / Adam Alexander T. Smith / Gavriel Olshansky / Brian G. Drew / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Matthias Arnold / Kwangsik Nho /
    Andrew J. Saykin / Rebecca Baillie / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / Peter J. Meikle

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma ... ...

    Abstract The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

    Kevin Huynh / Wei Ling Florence Lim / Corey Giles / Kaushala S. Jayawardana / Agus Salim / Natalie A. Mellett / Adam Alexander T. Smith / Gavriel Olshansky / Brian G. Drew / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Matthias Arnold / Kwangsik Nho /
    Andrew J. Saykin / Rebecca Baillie / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / Peter J. Meikle

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma ... ...

    Abstract The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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