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Journal of Alzheimer's Disease: JAD

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https://www.readbyqxmd.com/read/29226873/modeling-prion-like-processing-of%C3%A2-tau%C3%A2-protein-in-alzheimer-s-disease-for%C3%A2-pharmaceutical-development
#1
Claude M Wischik, Björn O Schelter, Damon J Wischik, John M D Storey, Charles R Harrington
 Following our discovery of a fragment from the repeat domain of tau protein as a structural constituent of the PHF-core in Alzheimer's disease (AD), we developed an assay that captured several key features of the aggregation process. Tau-tau binding through the core tau fragment could be blocked by the same diaminophenothiazines found to dissolve proteolytically stable PHFs isolated from AD brain. We found that the PHF-core tau fragment is inherently capable of auto-catalytic self-propagation in vitro, or "prion-like processing", that has now been demonstrated for several neurodegenerative disorders...
December 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226870/alzheimer-s-disease-progression-factors-influencing-cognitive-decline
#2
Camilla Ferrari, Gemma Lombardi, Cristina Polito, Giulia Lucidi, Silvia Bagnoli, Irene Piaceri, Benedetta Nacmias, Valentina Berti, Debora Rizzuto, Laura Fratiglioni, Sandro Sorbi
BACKGROUND: Alzheimer's disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors. OBJECTIVE: The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients...
December 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226869/the-heritability-of-frontotemporal-lobar-degeneration-validation-of-pedigree-classification-criteria-in-a-northern-italy-cohort
#3
Silvia Fostinelli, Miriam Ciani, Roberta Zanardini, Orazio Zanetti, Giuliano Binetti, Roberta Ghidoni, Luisa Benussi
A large portion of frontotemporal lobar degeneration (FTLD) patients has a family history of disease and the presence of a pathogenic mutation confirms the clinical diagnosis. Recently, standardized criteria to evaluate FTLD pedigree, based on first- and second-degree affected relatives, their age at onset, and clinical phenotype, were proposed and validated in an American cohort. Herein we applied these criteria to 402 Italian FTLD pedigrees and assessed mutation frequencies in GRN, C9orf72, and MAPT genes with the aim of validating these criteria...
December 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226863/associations-between-use-of-specific-analgesics-and-concentrations-of-amyloid-%C3%AE-42-or-phospho-tau-in-regions-of-human-cerebral-cortex
#4
Margaret E Flanagan, Eric B Larson, Rod L Walker, C Dirk Keene, Nadia Postupna, Brenna Cholerton, Joshua A Sonnen, Sascha Dublin, Paul K Crane, Thomas J Montine
Analgesics are commonly used by older adults, raising the question of whether their use might contribute to dementia risk and neuropathologic changes of Alzheimer's disease (AD). The Adult Changes in Thought (ACT) study is a population-based study of brain aging and incident dementia among people 65 years or older who are community dwelling and not demented at entry. Amyloid-β (Aβ)42 and phospho-tau were quantified using Histelide in regions of cerebral cortex from 420 brain autopsies. Total standard daily doses of prescription opioid and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure during a defined 10-year exposure window were identified using automated pharmacy dispensing data and used to classify people as having no/low, intermediate, or high exposure...
December 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226877/negative-prospective-memory-in%C3%A2-alzheimer-s-disease-do-not-perform-that-action
#5
Mohamad El Haj, Yann Coello, Dimitrios Kapogiannis, Karim Gallouj, Pascal Antoine
Relatively to "standard" prospective memory, i.e., remembering to perform a future action, little is known about negative prospective memory, i.e., remembering not to perform a future action. This study investigated the latter ability in Alzheimer's disease (AD). AD participants and healthy older adults were asked to click on the keyboard or not to click on it when a cue word was encountered. Results showed more omissions (i.e., forgetting to click the keyboard when the instruction was to do so) in AD participants than in healthy older adults, suggesting a prospective memory deficit...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226875/vegfr1-and-vegfr2-in-alzheimer-s-disease
#6
Rachel Harris, James Scott Miners, Shelley Allen, Seth Love
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Despite upregulation of VEGF in the brain in Alzheimer's disease (AD), probably in response to amyloid-β, vasoconstriction, and tissue hypoxia, there is no consequent increase in microvessel density. VEGF binds to and activates VEGF receptor 2 (VEGFR2), but also binds to VEGF receptor 1 (VEGFR1), which exists in less-active membrane-bound and inactive soluble (sVEGFR1) forms and inhibits pro-angiogenic signaling. We have investigated whether altered expression of VEGF receptors might account for the lack of angiogenic response to VEGF in AD...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226868/predictors-of-age-of-diagnosis-and-survival-of-alzheimer-s-disease-in-down-syndrome
#7
Amanda Sinai, Claire Mokrysz, Jane Bernal, Ingrid Bohnen, Simon Bonell, Ken Courtenay, Karen Dodd, Dina Gazizova, Angela Hassiotis, Richard Hillier, Judith McBrien, Jane McCarthy, Kamalika Mukherji, Asim Naeem, Natalia Perez-Achiaga, Khadija Rantell, Vijaya Sharma, David Thomas, Zuzana Walker, Sarah Whitham, Andre Strydom
BACKGROUND: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer's disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade. OBJECTIVE: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these. METHODS: Data was obtained from the Aging with Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting of data extracted from clinical records of patients seen by Community Intellectual Disability Services (CIDS) in England...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226867/an-objective-method-to-accurately-measure-cardiorespiratory-fitness-in-older-adults-who-cannot-satisfy-widely-used-oxygen-consumption-criteria
#8
Ryan J Dougherty, Jacob B Lindheimer, Aaron J Stegner, Stephanie Van Riper, Ozioma C Okonkwo, Dane B Cook
Cardiorespiratory fitness (CRF) is routinely investigated in older adults; however, the most appropriate CRF measure to use for this population has received inadequate attention. This study aimed to 1) evaluate the reliability and validity of the oxygen uptake efficiency slope (OUES) as a sub-maximal measurement of CRF; 2) examine demographic, risk-factor, and exercise testing differences in older adults who satisfied standardized criteria for a peak oxygen consumption (V̇O2peak) test compared to those who did not; and 3) determine the difference between directly measured V̇O2peak values and OUES-predicted V̇O2peak values...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226866/11c-cft-pet-in-presymptomatic-ftdp-17-a-potential-biomarker-predicting-onset
#9
Liyong Wu, Jia Liu, Xueyan Feng, Jing Dong, Wei Qin, Yang Liu, Jingjuan Wang, Jie Lu, Kewei Chen, Yuping Wang, Jianping Jia
Frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17) is a rare autosomal dominant neurodegenerative disorder. Most patients with FTDP-17 carry the mutation in the microtubule-associated protein tau (MAPT) gene. Striatum is predominantly and early affected in FTDP-17. Five family members (two symptomatic patients and three presymptomatic mutation carriers) from a Chinese pedigree of FTDP-17 with N279K mutation in MAPT were enrolled. Parkinsonism was the initial symptom for symptomatic patients...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226865/sirt1-deacetylates-sc35-and-suppresses-its-function-in-tau-exon-10-inclusion
#10
Xiaomin Yin, Xiaosu Jiang, Jia Wang, Shuo Qian, Fei Liu, Wei Qian
Approximately equal amounts of 3R-tau and 4R-tau resulting from alternative splicing of tau exon 10 is necessary to maintain normal brain function. Dysregulation of alternative splicing of tau exon 10 and the imbalance of 3R-tau/4R-tau have been seen in inherited and sporadic tauopathies. Splicing factor SC35 (also name as SRSF2) plays an important role in promoting tau exon 10 inclusion. SC35 is post-translationally modified by phosphorylation and acetylation, but the role of acetylation in SC35-medicated tau exon 10 inclusion is unknown...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226864/cardiorespiratory-fitness-and-white-matter-neuronal-fiber-integrity-in-mild-cognitive-impairment
#11
Kan Ding, Takashi Tarumi, David C Zhu, Benjamin Tseng, Binu P Thomas, Marcel Turner, Justin Repshas, Diana R Kerwin, Kyle B Womack, Hanzhang Lu, C Munro Cullum, Rong Zhang
BACKGROUND: Mounting evidence showed the self-reported levels of physical activity are positively associated with white matter (WM) integrity and cognitive performance in normal adults and patients with mild cognitive impairment (MCI). However, the objective measure of cardiorespiratory fitness (CRF) was not used in these studies. OBJECTIVE: To determine the associations of CRF measured by maximal oxygen uptake (VO2max) with WM fiber integrity and neurocognitive performance in older adults with MCI...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226862/the-rationale-and-design-of-the-reducing-pathology-in-alzheimer-s-disease-through-angiotensin-targeting-radar-trial
#12
Patrick G Kehoe, Peter S Blair, Beth Howden, David L Thomas, Ian B Malone, Jeremy Horwood, Clare Clement, Lucy Selman, Hannah Baber, Athene Lane, Elizabeth Coulthard, Anthony Peter Passmore, Nick C Fox, Ian B Wilkinson, Yoav Ben-Shlomo
BACKGROUND: Anti-hypertensives that modify the renin angiotensin system may reduce Alzheimer's disease (AD) pathology and reduce the rate of disease progression. OBJECTIVE: To conduct a phase II, two arm, double-blind, placebo-controlled, randomized trial (ISRCTN: 93682878; EudraCT: 2012-003641-15) of losartan to test the efficacy of Reducing pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR). METHODS: Men and women aged at least 55 years with mild-to-moderate AD will be randomly allocated 100 mg encapsulated generic losartan or placebo once daily for 12 months after successful completion of a 2-week open-label phase and 2-week placebo washout to establish drug tolerability...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226872/while-i-still-remember-30-years-of-alzheimer-s-disease-research
#13
Thomas B Shea
Turns out I have been a major contributor to the Journal of Alzheimer's Disease over its 20-year history. As such, I was invited to provide a review of my work over the years. What follows is a retrospective of how the Alzheimer-related research of a Ph.D. (i.e., not an M.D.) transitioned from basic to clinical, and moved from bench to bedside and back again.I have included some of the more humorous and poignant twists along the way that some older players may find familiar and I hope might inspire some younger players to hang in there...
December 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226871/increased-serum-acylated-ghrelin-levels-in%C3%A2-patients-with-mild-cognitive-impairment
#14
Xi Cao, Min Zhu, Yan He, Wenzheng Chu, Yifeng Du, Heng Du
Ghrelin is a stomach-derived circulating hormone. In addition to its function as an orexigenic stimulant, the role of ghrelin in the consolidation of learning and memory has been implicated in recent years. However, the status of circulating acylated ghrelin (AG, that is, the functional form of ghrelin) in the symptomatic predementia stage of Alzheimer's disease (AD) has rarely been investigated. In the current study, we examined the serum levels of acylated and total ghrelin in 22 patients with mild cognitive impairment (MCI) and 30 cognitively normal controls...
December 2, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226876/serum-c-peptide-visfatin-resistin-and-ghrelin-are-altered-in-sporadic-and-grn-associated-frontotemporal-lobar-degeneration
#15
Roberta Zanardini, Luisa Benussi, Silvia Fostinelli, Claudia Saraceno, Miriam Ciani, Barbara Borroni, Alessandro Padovani, Giuliano Binetti, Roberta Ghidoni
Frontotemporal lobar degeneration (FTLD) is a group of complex neurodegenerative disease characterized by progressive deterioration of the frontal and anterior temporal lobes of the brain resulting in different heterogeneous conditions, mainly characterized by personality changes, behavioral disturbances, such as binge eating, and deficits in language and executive functions. Null mutations in progranulin gene (GRN) are one of the most frequent genetic determinants in familial frontotemporal dementia. Recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance revealing its metabolic function...
December 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226874/alterations-in-acrolein-metabolism-contribute-to-alzheimer-s-disease
#16
Han-Hsing Tsou, Wen-Chin Hsu, Jong-Ling Fuh, Shih-Pin Chen, Tsung-Yun Liu, Hsiang-Tsui Wang
Alzheimer's disease (AD) is a detrimental neurodegenerative disease, and early diagnosis appears to be the key to successful treatment. Acrolein, a byproduct of lipid peroxidation, has been shown to contribute to the pathological process of AD. This study recruited 118 elderly subjects consisting of 58 non-demented control subjects and 62 AD patients. We analyzed the acrolein-related metabolites in the plasma, cerebrospinal fluid (CSF), and urine of all subjects. We found that the levels of acrolein-conjugated protein (Acr-PC) in the plasma (p = 0...
December 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226861/neuroanatomical-comparison-of-the-word-and-picture-versions-of-the-free-and-cued-selective-reminding-test-in-alzheimer-s-disease
#17
Andrea Slachevsky, Paulo Barraza, Michael Hornberger, Carlos Muñoz-Neira, Emma Flanagan, Fernando Henríquez, Eduardo Bravo, Mauricio Farías, Carolina Delgado
Episodic memory tests with cued recall, such as the Free and Cued Selective Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal atrophy contributions to memory performance in Alzheimer's disease (AD). Both Word and Picture versions of the test exist but show different profiles, with the Picture version usually scoring higher across different cohorts. One possible explanation for this divergent performance between the different modality versions of the test might be that they rely on different sets of neural correlates...
December 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29172002/mental-states-in-moving-shapes-distinct%C3%A2-cortical-and-subcortical-contributions-to-theory-of-mind-impairments-in-dementia
#18
Artemis Synn, Annu Mothakunnel, Fiona Kumfor, Yu Chen, Olivier Piguet, John R Hodges, Muireann Irish
Impaired capacity for Theory of Mind (ToM) represents one of the hallmark features of the behavioral variant of frontotemporal dementia (bvFTD) and is suggested to underpin an array of socioemotional disturbances characteristic of this disorder. In contrast, while social processing typically remains intact in Alzheimer's disease (AD), the cognitive loading of socioemotional tasks may adversely impact mentalizing performance in AD. Here, we employed the Frith-Happé animations as a dynamic on-line assessment of mentalizing capacity with reduced incidental task demands in 18 bvFTD, 18 AD, and 25 age-matched Controls...
November 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29172001/co-expression-of-glia-maturation-factor%C3%A2-and-apolipoprotein-e4-in%C3%A2-alzheimer-s-disease-brain
#19
Ramasamy Thangavel, Sachin M Bhagavan, Swathi Beladakere Ramaswamy, Spurthi Surpur, Raghav Govindarajan, Duraisamy Kempuraj, Smita Zaheer, Sudhanshu Raikwar, Mohammad E Ahmed, Govindhasamy Pushpavathi Selvakumar, Shankar S Iyer, Asgar Zaheer
Apolipoprotein E4 (ApoE4) is a major genetic risk factor for Alzheimer's disease (AD). The E4 allele of ApoE plays a crucial role in the inflammatory and neurodegenerative processes associated with AD. This is evident from the multiple effects of the ApoE isoforms in amyloid-β (Aβ) aggregation. Glia maturation factor (GMF) is a brain-specific neuroinflammatory protein that we have previously demonstrated to be significantly upregulated in various regions of AD brains compared to non-AD control brains and that it induces neurodegeneration...
November 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29172000/translational-research-in-alzheimer-s-and-prion-diseases
#20
Giuseppe Di Fede, Giorgio Giaccone, Mario Salmona, Fabrizio Tagliavini
Translational neuroscience integrates the knowledge derived by basic neuroscience with the development of new diagnostic and therapeutic tools that may be applied to clinical practice in neurological diseases. This information can be used to improve clinical trial designs and outcomes that will accelerate drug development, and to discover novel biomarkers which can be efficiently employed to early recognize neurological disorders and provide information regarding the effects of drugs on the underlying disease biology...
November 20, 2017: Journal of Alzheimer's Disease: JAD
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