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https://www.readbyqxmd.com/read/28738188/sleep-characteristics-and-risk-of-dementia-and-alzheimer-s-disease-the-atherosclerosis-risk-in-communities-study
#1
Pamela L Lutsey, Jeffrey R Misialek, Thomas H Mosley, Rebecca F Gottesman, Naresh M Punjabi, Eyal Shahar, Richard MacLehose, Rachel P Ogilvie, David Knopman, Alvaro Alonso
INTRODUCTION: This study tested the hypotheses that late-midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia for more than 15 years of follow-up. METHODS: A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in-home polysomnography (1996-1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996-2012) and (2) a comprehensive neurocognitive examination (2011-2013) with adjudication...
July 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28738187/presymptomatic-atrophy-in-autosomal-dominant-alzheimer-s-disease-a%C3%A2-serial-mri-study
#2
Kirsi M Kinnunen, David M Cash, Teresa Poole, Chris Frost, Tammie L S Benzinger, R Laila Ahsan, Kelvin K Leung, M Jorge Cardoso, Marc Modat, Ian B Malone, John C Morris, Randall J Bateman, Daniel S Marcus, Alison Goate, Stephen Salloway, Stephen Correia, Reisa A Sperling, Jasmeer P Chhatwal, Richard Mayeux, Adam M Brickman, Ralph N Martins, Martin R Farlow, Bernardino Ghetti, Andrew J Saykin, Clifford R Jack, Peter R Schofield, Eric McDade, Michael W Weiner, John M Ringman, Paul M Thompson, Colin L Masters, Christopher C Rowe, Martin N Rossor, Sebastien Ourselin, Nick C Fox
INTRODUCTION: Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. METHODS: Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point...
July 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28738127/early-onset-alzheimer-disease-and-candidate-risk-genes-involved-in-endolysosomal-transport
#3
Brian W Kunkle, Badri N Vardarajan, Adam C Naj, Patrice L Whitehead, Sophie Rolati, Susan Slifer, Regina M Carney, Michael L Cuccaro, Jeffery M Vance, John R Gilbert, Li-San Wang, Lindsay A Farrer, Christiane Reitz, Jonathan L Haines, Gary W Beecham, Eden R Martin, Gerard D Schellenberg, Richard P Mayeux, Margaret A Pericak-Vance
Importance: Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. Objective: To search for rare variants contributing to the risk for EOAD. Design, Setting, and Participants: In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset <65 years) and 19 Caribbean Hispanic families previously screened as negative for established APP, PSEN1, and PSEN2 causal variants...
July 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28738114/i-spy-2-breast-cancer-trial-as-a-model-for-innovation-in-alzheimer-disease-therapies
#4
Mindi F Messmer, Erin E Wilhelm, Ira Shoulson
No abstract text is available yet for this article.
July 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28737945/preliminary-pet-study-of-18-f-fc119s-in-normal-and-alzheimer-s-disease-models
#5
Se Jong Oh, Min Hwan Kim, Sang Jin Han, Kyung Jun Kang, In Ok Ko, YoungSoo Kim, Ji Ae Park, Jae Yong Choi, Kyo Chul Lee, Dae Yoon Chi, Yong Jin Lee, Kyeong Min Kim
To evaluate the efficacy of (18)F-FC119S as a positron emission tomography (PET) radiopharmaceutical for the imaging of Alzheimer's disease (AD), we studied the drug absorption characteristics and (18)F-FC119S distribution in normal mice. In addition, we evaluated the specificity of (18)F-FC119S for β-amyloid (Aβ) in the AD group of an APP/PS1 mouse model and compared it with that in the wild-type (WT) group. (18)F-FC119S exhibited the characteristics of rapid brain uptake and washout patterns in the normal mice...
July 24, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28737894/dual-role-of-gold-nanorods-inhibition-dissolution-of-a%C3%AE-fibrils-induced-by-near-ir-laser
#6
Swathi Sudhakar, Poornima Budime Santhosh, Ethayaraja Mani
Extracellular plaques of amyloid beta (Aβ) fibrils and neurofibrillary tangles are known to be associated with neurological diseases such as Alzheimer's. Studies have shown that spherical nanoparticles inhibit the formation of Aβ fibrils by intercepting the nucleation and growth pathways of fibrillation. In this report, gold nanorods (AuNR) are used to inhibit the formation of Aβ fibrils and the shape-dependent plasmonic properties of AuNR are exploited to faciliate faster dissolution of mature Aβ fibrils...
July 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28737890/a-difluoroboron-%C3%AE-diketonate-probe-shows-turn-on-near-infrared-fluorescence-specific-for-tau-fibrils
#7
Kwang-Su Park, Mi Kyoung Kim, Yujin Seo, Taewoong Ha, Kyeongha Yoo, Seung Jae Hyeon, Yu Jin Hwang, Junghee Lee, Hoon Ryu, Hyunah Choo, Youhoon Chong
Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimer's disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, non-invasive imaging of tau aggregates has been highlighted as a promising diagnostic tool for AD. We have previously identified a tau-specific "turn-on" near-infrared fluorescent (NIRF) probe (1) and, in this study, structural modification was performed to optimize its physicochemical as well as fluorescence properties...
July 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28737885/classics-in-chemical-neuroscience-memantine
#8
Shahrina Alam, Kaelyn Skye Lingenfelter, Aaron M Bender, Craig W Lindsley
Memantine was the first breakthrough medication for the treatment of moderate to severe Alzheimer's disease (AD) patients, and represents a fundamentally new mechanism of action (moderate-affinity, uncompetitive, voltage-dependent, N-methyl-D-aspartate (NMDA) receptor antagonist that exhibits fast on/off kinetics) to modulate glutamatergic dysfunction. Since its approval by the FDA in 2003, memantine, alone, and in combination with donepezil, has improved patient outcomes in terms of cognition, behavioral disturbances, daily functioning and delaying time to institutionalization...
July 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28737807/npy-binds-with-heme-to-form-a-npy-heme-complex-enhancing-peroxidase-activity-in-free-heme-and-promoting-npy-nitration-and-inactivation
#9
Huixian Ye, Zhen Yang, Hailing Li, Zhonghong Gao
Neuropeptide Y (NPY) is a member of the pancreatic peptide family of neuropeptides that play a crucial role in numerous central and peripheral nervous system responses. Recently, it has been shown that NPY protects cells against neurotoxic damage from β-amyloid peptides (Aβ) in Alzheimer's disease (AD). Heme is a common factor linking several metabolic perturbations in AD and altered heme metabolism has been shown to be related to the pathologies of AD. Thus, heme may have a chance to act on NPY and potentially counteract its function...
July 24, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28737514/bag3-plays-a-central-role-in-proteostasis-in-the-heart
#10
Wataru Mizushima, Junichi Sadoshima
Proteinopathies are characterized by the accumulation of misfolded proteins, which ultimately interfere with normal cell function. While neurological diseases, such as Huntington disease and Alzheimer disease, are well-characterized proteinopathies, cardiac diseases have recently been associated with alterations in proteostasis. In this issue of the JCI, Fang and colleagues demonstrate that mice with cardiac-specific deficiency of the co-chaperone protein BCL2-associated athanogene 3 (BAG3) develop dilated cardiomyopathy that is associated with a destabilization of small HSPs as the result of a disrupted interaction between BAG3 and HSP70...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28737295/towards-a-unified-analysis-of-brain-maturation-and-aging-across-the-entire-lifespan-a-mri-analysis
#11
Pierrick Coupé, Gwenaelle Catheline, Enrique Lanuza, José Vicente Manjón
There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained...
July 24, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28737118/subjective-cognitive-decline-is-longitudinally-associated-with-lower-health-related-quality-of-life
#12
Susanne Roehr, Tobias Luck, Alexander Pabst, Horst Bickel, Hans-Helmut König, Dagmar Lühmann, Angela Fuchs, Steffen Wolfsgruber, Birgitt Wiese, Siegfried Weyerer, Edelgard Mösch, Christian Brettschneider, Tina Mallon, Michael Pentzek, Michael Wagner, Silke Mamone, Jochen Werle, Martin Scherer, Wolfgang Maier, Frank Jessen, Steffi G Riedel-Heller
BACKGROUND: Subjective cognitive decline (SCD), the potentially earliest notable manifestation of preclinical Alzheimer's disease and other dementias, was consistently associated with lower quality of life in cross-sectional studies. The aim of this study was to investigate whether such an association persists longitudinally - particularly with health-related quality of life (HRQoL) in older individuals without cognitive impairment. METHODS: Data were derived from follow-up 2-6 of the prospective Germany Study on Ageing, Cognition and Dementia in Primary Care (AgeCoDe) covering a total six-year observation period...
July 24, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28737113/micrornas-roles-in-regulating-neuroinflammation
#13
Andrew D Gaudet, Laura K Fonken, Linda R Watkins, Randy J Nelson, Phillip G Popovich
MicroRNAs (miRNAs) are small noncoding RNAs that broadly affect cellular and physiological function in all multicellular organisms. Here, the role of miRNAs in neuroinflammation is considered. miRNAs are 21- to 23-oligonucleotide RNAs that regulate translation of specific RNAs by binding to complementary regulatory RNA sequences, thereby causing mRNA degradation or sequestration. More than 5000 miRNAs likely exist in humans, and each miRNA binds an average of 200 RNAs. Specific immunomodulatory miRNAs can regulate a set of RNAs in a coordinated manner, suggesting that effective miRNA-based therapeutic manipulations for neuroinflammatory conditions may be revealed...
July 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28736899/trajectories-of-depressive-and-anxiety-symptoms-in-older-adults-a-6-year-prospective-cohort-study
#14
Sophie E Holmes, Irina Esterlis, Carolyn M Mazure, Yen Ying Lim, David Ames, Stephanie Rainey-Smith, Chris Fowler, Kathryn Ellis, Ralph N Martins, Olivier Salvado, Vincent Doré, Victor L Villemagne, Christopher C Rowe, Simon M Laws, Colin L Masters, Robert H Pietrzak, Paul Maruff
OBJECTIVE: Depressive and anxiety symptoms are common in older adults, significantly affect quality of life, and are risk factors for Alzheimer's disease. We sought to identify the determinants of predominant trajectories of depressive and anxiety symptoms in cognitively normal older adults. METHOD: Four hundred twenty-three older adults recruited from the general community underwent Aβ positron emission tomography imaging, apolipoprotein and brain-derived neurotrophic factor genotyping, and cognitive testing at baseline and had follow-up assessments...
July 24, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28736792/double-injected-human-stem-cells-enhance-rehabilitation-in-tbi-mice-via-modulation-of-survival-and-inflammation
#15
Chul Kim, Ji-Min Park, TaeHo Kong, Seungmin Lee, Ki-Weon Seo, Yuri Choi, Young Sook Song, Jisook Moon
Traumatic brain injury (TBI), a complicated form of brain damage, is a major cause of mortality in adults. Following mechanical and structural primary insults, a battery of secondary insults, including neurotransmitter-mediated cytotoxicity, dysregulation of calcium and macromolecule homeostasis, and increased oxidative stress, exacerbate brain injury and functional deficits. Although stem cell therapy is considered to be an alternative treatment for brain injuries, such as TBI and stroke, many obstacles remain...
July 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28736551/differential-phenotypes-of-myeloid-derived-suppressor-and-t-regulatory-cells-and-cytokine-levels-in-amnestic-mild-cognitive-impairment-subjects-compared-to-mild-alzheimer-diseased-patients
#16
Aurélie Le Page, Hugo Garneau, Gilles Dupuis, Eric H Frost, Anis Larbi, Jacek M Witkowski, Graham Pawelec, Tamàs Fülöp
Alzheimer disease (AD) is the most prevalent form of dementia although the underlying cause(s) remains unknown at this time. However, neuroinflammation is believed to play an important role and suspected contributing immune parameters can be revealed in studies comparing patients at the stage of amnestic mild cognitive impairment (aMCI) to healthy age-matched individuals. A network of immune regulatory cells including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) maintains immune homeostasis but there are very few data on the role of these cells in AD...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736521/group-level-progressive-alterations-in-brain-connectivity-patterns-revealed-by-diffusion-tensor-brain-networks-across-severity-stages-in-alzheimer-s-disease
#17
Javier Rasero, Carmen Alonso-Montes, Ibai Diez, Laiene Olabarrieta-Landa, Lakhdar Remaki, Iñaki Escudero, Beatriz Mateos, Paolo Bonifazi, Manuel Fernandez, Juan Carlos Arango-Lasprilla, Sebastiano Stramaglia, Jesus M Cortes
Alzheimer's disease (AD) is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer's Disease Neuroimaging Initiative (ADNI), four different groups were defined (all of them matched by age, sex and education level): G1 (N1 = 36, healthy control subjects, Control), G2 (N2 = 36, early mild cognitive impairment, EMCI), G3 (N3 = 36, late mild cognitive impairment, LMCI) and G4 (N4 = 36, AD)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28736311/imaging-wide-association-study-integrating-imaging-endophenotypes-in-gwas
#18
Zhiyuan Xu, Chong Wu, Wei Pan
A new and powerful approach, called imaging-wide association study (IWAS), is proposed to integrate imaging endophenotypes with GWAS to boost statistical power and enhance biological interpretation for GWAS discoveries. IWAS extends the promising transcriptome-wide association study (TWAS) from using gene expression endophenotypes to using imaging and other endophenotypes with a much wider range of possible applications. As illustration, we use gray-matter volumes of several brain regions of interest (ROIs) drawn from the ADNI-1 structural MRI data as imaging endophenotypes, which are then applied to the individual-level GWAS data of ADNI-GO/2 and a large meta-analyzed GWAS summary statistics dataset (based on about 74,000 individuals), uncovering some novel genes significantly associated with Alzheimer's disease (AD)...
July 20, 2017: NeuroImage
https://www.readbyqxmd.com/read/28736294/enhanced-neuroprotection-of-anthocyanin-loaded-peg-gold-nanoparticles-against-a%C3%AE-1-42-induced-neuroinflammation-and-neurodegeneration-via-the-nf-kb-jnk-gsk3%C3%AE-signaling-pathway
#19
Min Ju Kim, Shafiq Ur Rehman, Faiz Ul Amin, Myeong Ok Kim
Amyloid-beta (Aβ1-42) plaques and neurofibrillary tangles (NFTs) are the main hallmarks considered to be associated with neuroinflammation in Alzheimer's disease (AD). Recently, nanoparticle-based targeted drug delivery approaches have been found to be a useful tool in the neurotherapeutics field. Therefore, we examined and compared the neuroprotective effect of anthocyanins alone and anthocyanin-loaded poly (ethylene glycol)-gold nanoparticles (PEG-AuNPs) in Aβ1-42-injected mouse and in vitro models of AD...
July 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28735144/entorhinal-tau-pathology-disrupts-hippocampal-prefrontal-oscillatory-coupling-during-associative-learning
#20
Stephanie E Tanninen, Bardia Nouriziabari, Mark D Morrissey, Rami Bakir, Robert D Dayton, Ronald L Klein, Kaori Takehara-Nishiuchi
A neural signature of asymptomatic preclinical Alzheimer's disease (AD) is disrupted connectivity between brain regions; however, its underlying mechanisms remain unknown. Here, we tested whether a preclinical pathologic feature, tau aggregation in the entorhinal cortex (EC) is sufficient to disrupt the coordination of local field potentials (LFPs) between its efferent regions. P301L-mutant human tau or green fluorescent protein (GFP) was virally overexpressed in the EC of adult rats. LFPs were recorded from the dorsal hippocampus and prelimbic medial prefrontal cortex while the rats underwent trace eyeblink conditioning where they learned to associate 2 stimuli separated by a short time interval...
July 6, 2017: Neurobiology of Aging
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