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https://www.readbyqxmd.com/read/28641921/genome-wide-association-and-interaction-studies-of-csf-t-tau-a%C3%AE-42-ratio-in-adni-cohort
#1
Jin Li, Qiushi Zhang, Feng Chen, Xianglian Meng, Wenjie Liu, Dandan Chen, Jingwen Yan, Sungeun Kim, Lei Wang, Weixing Feng, Andrew J Saykin, Hong Liang, Li Shen
The pathogenic relevance in Alzheimer's disease (AD) presents a decrease of cerebrospinal fluid amyloid-ß42 (Aß42) burden and an increase in cerebrospinal fluid total tau (T-tau) levels. In this work, we performed genome-wide association study (GWAS) and genome-wide interaction study of T-tau/Aß42 ratio as an AD imaging quantitative trait on 843 subjects and 563,980 single-nucleotide polymorphisms (SNPs) in ADNI cohort. We aim to identify not only SNPs with significant main effects but also SNPs with interaction effects to help explain "missing heritability"...
May 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#2
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#3
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28633142/multifactorial-analysis-of-a-biomarker-pool-for-alzheimer-disease-risk-in-a-north-indian-population
#4
Puneet Talwar, Sandeep Grover, Juhi Sinha, Puneet Chandna, Rachna Agarwal, Suman Kushwaha, Ritushree Kukreti
BACKGROUND: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. METHODS: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. RESULTS: The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0...
June 21, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28630235/ultrasound-markers-of-carotid-atherosclerosis-and-cognition-the-northern-manhattan-study
#5
Hannah Gardener, Michelle R Caunca, Chuanhui Dong, Ying Kuen Cheung, Mitchell S V Elkind, Ralph L Sacco, Tatjana Rundek, Clinton B Wright
BACKGROUND AND PURPOSE: Ultrasound markers of carotid atherosclerosis may be related to cognitive status. We hypothesized that individuals with greater carotid intima-media thickness (cIMT) and carotid plaque burden would exhibit worse cognition. METHODS: One thousand one hundred sixty-six stroke-free participants from the NOMAS (Northern Manhattan Study) underwent carotid ultrasound and neuropsychological examination. Among them, 826 underwent a second neuropsychological examination an average of 5 years later...
June 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28629965/%C3%A2-cortical-atrophy-is-associated-with-accelerated-cognitive-decline-in-mild-cognitive-impairment-with-subsyndromal-depression
#6
Mitzi M Gonzales, Philip S Insel, Craig Nelson, Duygu Tosun, Niklas Mattsson, Susanne G Mueller, Simona Sacuiu, David Bickford, Michael W Weiner, R Scott Mackin
OBJECTIVES: To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period. DESIGN: Prospective cohort study. SETTING: Multicenter, clinic-based. PARTICIPANTS: Within the Alzheimer's Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points...
April 20, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28628634/protein-signature-in-cerebrospinal-fluid-and-serum-of-alzheimer-s-disease-patients-the-case-of-apolipoprotein-a-1-proteoforms
#7
Chiara Fania, Beatrice Arosio, Daniele Capitanio, Enrica Torretta, Cristina Gussago, Evelyn Ferri, Daniela Mari, Cecilia Gelfi
In the diagnosis of Alzheimer's disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha β-amyloid (Aβ) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecules for AD diagnosis and monitoring in CSF is hampered by several "confounding" factors including intra- and inter-individual, pre-analytical and analytical variabilities...
2017: PloS One
https://www.readbyqxmd.com/read/28626864/detecting-genetic-association-through-shortest-paths-in-a-bidirected-graph
#8
Masao Ueki, Yoshinori Kawasaki, Gen Tamiya
Genome-wide association studies (GWASs) commonly use marginal association tests for each single-nucleotide polymorphism (SNP). Because these tests treat SNPs as independent, their power will be suboptimal for detecting SNPs hidden by linkage disequilibrium (LD). One way to improve power is to use a multiple regression model. However, the large number of SNPs preclude simultaneous fitting with multiple regression, and subset regression is infeasible because of an exorbitant number of candidate subsets. We therefore propose a new method for detecting hidden SNPs having significant yet weak marginal association in a multiple regression model...
June 19, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28626809/epidermal-growth-factor-prevents-apoe4-induced-cognitive-and-cerebrovascular-deficits-in-female-mice
#9
Riya Thomas, Alan W J Morris, Leon M Tai
Cerebrovascular dysfunction is re-emerging as a major component of aging, and may contribute to the risk of developing Alzheimer's disease (AD). Two important risk factors for cerebrovascular dysfunction are APOE and female sex, which are primarily researched in the context of high amyloid-β (Aβ) levels as found in AD. However, APOE4 and sex modulate Aβ-independent pathways that may induce cerebrovascular dysfunction as a downstream consequence. Therefore, testing the activity of factors that target cerebrovascular dysfunction in Aβ-independent models that incorporate APOE4 and female sex is crucial...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#10
Loïc Dayon, Seu Ping Guiraud, John Corthésy, Laeticia Da Silva, Eugenia Migliavacca, Domilė Tautvydaitė, Aikaterini Oikonomidi, Barbara Moullet, Hugues Henry, Sylviane Métairon, Julien Marquis, Patrick Descombes, Sebastiano Collino, François-Pierre J Martin, Ivan Montoliu, Martin Kussmann, Jérôme Wojcik, Gene L Bowman, Julius Popp
BACKGROUND: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults...
June 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28623677/incidence-of-cognitively-defined-late-onset-alzheimer-s-dementia-subgroups-from-a-prospective-cohort-study
#11
Paul K Crane, Emily Trittschuh, Shubhabrata Mukherjee, Andrew J Saykin, R Elizabeth Sanders, Eric B Larson, Susan M McCurry, Wayne McCormick, James D Bowen, Thomas Grabowski, Mackenzie Moore, Julianna Bauman, Alden L Gross, C Dirk Keene, Thomas E Bird, Laura E Gibbons, Jesse Mez
INTRODUCTION: There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia. METHODS: We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments...
June 14, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28620701/chronic-cerebral-hypoperfusion-induced-synaptic-proteome-changes-in-the-rat-cerebral-cortex
#12
Katalin Völgyi, Péter Gulyássy, Mihail Ivilinov Todorov, Gina Puska, Kata Badics, Dávid Hlatky, Katalin Adrienna Kékesi, Gabriella Nyitrai, András Czurkó, László Drahos, Arpád Dobolyi
Chronic cerebral hypoperfusion (CCH) evokes mild cognitive impairment (MCI) and contributes to the progression of vascular dementia and Alzheimer's disease (AD). How CCH induces these neurodegenerative processes that may spread along the synaptic network and whether they are detectable at the synaptic proteome level of the cerebral cortex remains to be established. In the present study, we report the synaptic protein changes in the cerebral cortex after stepwise bilateral common carotid artery occlusion (BCCAO) induced CCH in the rat...
June 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28614836/visual-evaluation-of-medial-temporal-lobe-atrophy-as-a-clinical-marker-of-conversion-from-mild-cognitive-impairment-to-dementia-and-for-predicting-progression-in-patients-with-mild-cognitive-impairment-and-mild-alzheimer-s-disease
#13
Karin Persson, Maria Lage Barca, Rannveig Sakshaug Eldholm, Lena Cavallin, Jūratė Šaltytė Benth, Geir Selbæk, Anne Brækhus, Ingvild Saltvedt, Knut Engedal
BACKGROUND/AIMS: To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). METHODS: vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria...
June 15, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28612048/obesity-accelerates-alzheimer-related-pathology-in-apoe4-but-not-apoe3-mice
#14
V Alexandra Moser, Christian J Pike
Alzheimer's disease (AD) risk is modified by both genetic and environmental risk factors, which are believed to interact to cooperatively modify pathogenesis. Although numerous genetic and environmental risk factors for AD have been identified, relatively little is known about potential gene-environment interactions in regulating disease risk. The strongest genetic risk factor for late-onset AD is the ε4 allele of apolipoprotein E (APOE4). An important modifiable risk factor for AD is obesity, which has been shown to increase AD risk in humans and accelerate development of AD-related pathology in rodent models...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28601231/factors-affecting-therapeutic-response-to-rivastigmine-in-alzheimer-s-disease-patients-in-taiwan
#15
Tzu-Hua Chen, Mei-Chuan Chou, Chiou-Lian Lai, Shyh-Jong Wu, Chia-Ling Hsu, Yuan-Han Yang
Rivastigmine has been widely used in mild-to-moderate Alzheimer's disease (AD), but the therapeutic response rate varies from 20 to 60%. A dose-dependent effect has been suggested, but the plasma concentration of rivastigmine and its metabolite, NAP 226-90, were not measured in previous studies. The influencing factors of therapeutic response are complicated and discordant in various studies among different ethnic groups. Hence, we analyzed the therapeutic responses of rivastigmine, measured by neuropsychological assessments, among 63 clinically diagnosed AD patients taking a daily dosage of 6-9 mg in relation to their plasma concentration of rivastigmine and NAP 226-90, apolipoprotein E (APOE) genotype and demographic characteristics...
June 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28596117/disrupted-white-matter-structural-networks-in-healthy-older-adult-apoe-%C3%AE%C2%B54-carriers-an-international-multicenter-dti-study
#16
Enrica Cavedo, Simone Lista, Katrine Rojkova, Patrizia A Chiesa, Marion Houot, Katharina Brueggen, Janusch Blautzik, Arun L W Bokde, Bruno Dubois, Frederik Barkhof, Petra J W Pouwels, Stefan Teipel, Harald Hampel
The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE ε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics...
June 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28589856/association-analysis-of-rare-variants-near-the-apoe-region-with-csf-and-neuroimaging-biomarkers-of-alzheimer-s-disease
#17
Kwangsik Nho, Sungeun Kim, Emrin Horgusluoglu, Shannon L Risacher, Li Shen, Dokyoon Kim, Seunggeun Lee, Tatiana Foroud, Leslie M Shaw, John Q Trojanowski, Paul S Aisen, Ronald C Petersen, Clifford R Jack, Michael W Weiner, Robert C Green, Arthur W Toga, Andrew J Saykin
BACKGROUND: The APOE ε4 allele is the most significant common genetic risk factor for late-onset Alzheimer's disease (LOAD). The region surrounding APOE on chromosome 19 has also shown consistent association with LOAD. However, no common variants in the region remain significant after adjusting for APOE genotype. We report a rare variant association analysis of genes in the vicinity of APOE with cerebrospinal fluid (CSF) and neuroimaging biomarkers of LOAD. METHODS: Whole genome sequencing (WGS) was performed on 817 blood DNA samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI)...
May 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28588075/cerebral-perfusion-and-the-risk-of-dementia-a-population-based-study
#18
Frank J Wolters, Hazel I Zonneveld, Albert Hofman, Aad van der Lugt, Peter J Koudstaal, Meike W Vernooij, M Arfan Ikram
Background -Cerebral hypoperfusion has previously been associated with mild cognitive impairment and dementia in various cross-sectional studies, but whether hypoperfusion precedes neurodegeneration is unknown. We prospectively determined the association of cerebral perfusion with subsequent cognitive decline and development of dementia. Methods -Between 2005 and 2012, we measured cerebral blood flow by 2D phase-contrast magnetic resonance imaging (MRI) in non-demented participants of the population-based Rotterdam Study...
June 6, 2017: Circulation
https://www.readbyqxmd.com/read/28587659/glutaminyl-cyclase-activity-correlates-with-levels-of-a%C3%AE-peptides-and-mediators-of-angiogenesis-in-cerebrospinal-fluid-of-alzheimer-s-disease-patients
#19
Claire Bridel, Torsten Hoffmann, Antje Meyer, Sisi Durieux, Marleen A Koel-Simmelink, Matthias Orth, Philip Scheltens, Inge Lues, Charlotte E Teunissen
BACKGROUND: Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaques and reduction of pE-Aβ species is associated with improvement of cognitive tasks in animal models of Alzheimer's disease (AD). Pharmacological inhibition of QC has thus emerged as a promising therapeutic approach for AD...
June 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28582863/framingham-risk-score-and-the-risk-of-progression-from-mild-cognitive-impairment-to-dementia
#20
Giovanna Viticchi, Lorenzo Falsetti, Laura Buratti, Giulia Sajeva, Simona Luzzi, Marco Bartolini, Leandro Provinciali, Mauro Silvestrini
BACKGROUND: Mild cognitive impairment (MCI) often represents the clinical manifestation of cognitive deterioration preceding Alzheimer's disease (AD). Currently, there are no reliable approaches for an objective evaluation of the risk of developing AD in MCI patients. OBJECTIVE: The aim of this study was to verify whether the Framingham cardiovascular risk profile (FCRP) could be useful to identify patients at the highest risk of conversion from MCI to AD. METHODS: Patients with amnestic MCI (aMCI) were carefully investigated to assess their vascular risk profile...
May 27, 2017: Journal of Alzheimer's Disease: JAD
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