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https://www.readbyqxmd.com/read/28550246/plasma-tau-association-with-brain-atrophy-in-mild-cognitive-impairment-and-alzheimer-s-disease
#1
Kacie D Deters, Shannon L Risacher, Sungeun Kim, Kwangsik Nho, John D West, Kaj Blennow, Henrik Zetterberg, Leslie M Shaw, John Q Trojanowski, Michael W Weiner, Andrew J Saykin
BACKGROUND: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. OBJECTIVE: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. METHODS: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28539126/knowledge-driven-binning-approach-for-rare-variant-association-analysis-application-to-neuroimaging-biomarkers-in-alzheimer-s-disease
#2
Dokyoon Kim, Anna O Basile, Lisa Bang, Emrin Horgusluoglu, Seunggeun Lee, Marylyn D Ritchie, Andrew J Saykin, Kwangsik Nho
BACKGROUND: Rapid advancement of next generation sequencing technologies such as whole genome sequencing (WGS) has facilitated the search for genetic factors that influence disease risk in the field of human genetics. To identify rare variants associated with human diseases or traits, an efficient genome-wide binning approach is needed. In this study we developed a novel biological knowledge-based binning approach for rare-variant association analysis and then applied the approach to structural neuroimaging endophenotypes related to late-onset Alzheimer's disease (LOAD)...
May 18, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28538088/effects-of-the-insulin-sensitizer-metformin-in-alzheimer-disease-pilot-data-from-a-randomized-placebo-controlled-crossover-study
#3
Aaron M Koenig, Dawn Mechanic-Hamilton, Sharon X Xie, Martha F Combs, Anne R Cappola, Long Xie, John A Detre, David A Wolk, Steven E Arnold
Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system-penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers...
April 2017: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/28535786/biochemical-markers-in-vascular-cognitive-impairment-associated-with-subcortical-small-vessel-disease-a-consensus-report
#4
A Wallin, E Kapaki, M Boban, S Engelborghs, D M Hermann, B Huisa, M Jonsson, M G Kramberger, L Lossi, B Malojcic, S Mehrabian, A Merighi, E B Mukaetova-Ladinska, G P Paraskevas, B O Popescu, R Ravid, L Traykov, G Tsivgoulis, G Weinstein, A Korczyn, M Bjerke, G Rosenberg
BACKGROUND: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data...
May 23, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#5
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28527630/diagnostic-accuracy-of-csf-neurofilament-light-chain-protein-in-the-biomarker-guided-classification-system-for-alzheimer-s-disease
#6
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Roberto Floris, Francesco Garaci, Harald Hampel
We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein in the classification of patients with Alzheimer's disease (AD) and cognitively healthy control individuals (HCs) and patients with frontotemporal dementia (FTD) as comparisons. Particularly, we tested the performance of CSF NFL concentration in differentiating patient groups stratified by fluid biomarker profiles, independently of the severity of cognitive impairment (mild cognitive impairment (MCI) and AD dementia individuals), using a biomarker-guided descriptive classification system for AD...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28527215/diagnostic-and-prognostic-value-of%C3%A2-the%C3%A2-combination-of-two-measures-of%C3%A2-verbal-memory-in-mild-cognitive-impairment-due%C3%A2-to-alzheimer-s-disease
#7
Isabel Sala, Ignacio Illán-Gala, Daniel Alcolea, Ma Belén Sánchez-Saudinós, Sergio Andrés Salgado, Estrella Morenas-Rodríguez, Andrea Subirana, Laura Videla, Jordi Clarimón, María Carmona-Iragui, Roser Ribosa-Nogué, Rafael Blesa, Juan Fortea, Alberto Lleó
BACKGROUND: Episodic memory impairment is the core feature of typical Alzheimer's disease. OBJECTIVE: To evaluate the performance of two commonly used verbal memory tests to detect mild cognitive impairment due to Alzheimer's disease (MCI-AD) and to predict progression to Alzheimer's disease dementia (AD-d). METHODS: Prospective study of MCI patients in a tertiary memory disorder unit. Patients underwent an extensive neuropsychological battery including two tests of declarative verbal memory: The Free and Cued Selective Reminding Test (FCSRT) and the word list learning task from the Consortium to Establish a Registry for Alzheimer's disease (CERAD-WL)...
May 13, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527210/cerebrospinal-fluid-biomarkers-and-clinical-progression-in-patients-with-subjective-cognitive-decline-and-mild-cognitive-impairment
#8
Steffen Wolfsgruber, Alexandra Polcher, Alexander Koppara, Luca Kleineidam, Lutz Frölich, Oliver Peters, Michael Hüll, Eckart Rüther, Jens Wiltfang, Wolfgang Maier, Johannes Kornhuber, Piotr Lewczuk, Frank Jessen, Michael Wagner
BACKGROUND: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD). OBJECTIVE: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort...
May 13, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28521765/inhibition-of-o-glcnacase-leads-to-elevation-of-o-glcnac-tau-and-reduction-of-tauopathy-and-cerebrospinal-fluid-tau-in-rtg4510-mice
#9
Nicholas B Hastings, Xiaohai Wang, Lixin Song, Brent D Butts, Diane Grotz, Richard Hargreaves, J Fred Hess, Kwok-Lam Karen Hong, Cathy Ruey-Ruey Huang, Lynn Hyde, Maureen Laverty, Julie Lee, Diane Levitan, Sherry X Lu, Maureen Maguire, Veeravan Mahadomrongkul, Ernest J McEachern, Xuesong Ouyang, Thomas W Rosahl, Harold Selnick, Michaela Stanton, Giuseppe Terracina, David J Vocadlo, Ganfeng Wang, Joseph L Duffy, Eric M Parker, Lili Zhang
BACKGROUND: Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post-translational modification of tau that involves the addition of N-acetylglucosamine onto serine and threonine residues. Inhibition of O-GlcNAcase (OGA), the enzyme responsible for the removal of O-GlcNAc modification, has been shown to reduce tau pathology in several transgenic models...
May 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#10
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28513463/alzheimer-s-disease-against-peptides-products-of-enzymatic-cleavage-app-protein-biological-pathobiological-and-physico-chemical-properties-of-fibrillating-peptides
#11
Małgorzata Marszałek
Various peptides products of enzymatic cleavage of key for Alzheimer's disease Amyloid Precursor Protein (APP) are well known, but still are matter of scientific debate. The Aβ type products are especially challenging for experimental and medical research. This paper outlines several, still poorly known, biological and medical processes such as peptides biology, i.e., formation, biodistribution, translocation, transport and finally removal from brain compartments and body fluids like Intracellular Fluid (ICF), Cerebrospinal Fluid (CSF), Interstitial Fluid (ISF), blood serum or urine...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28505972/alzheimer-s-disease-associated-cerebrospinal-fluid-csf-biomarkers-do-not-correlate-with-csf-volumes-or-csf-production-rate
#12
Mikael Edsbagge, Ulf Andreasson, Khalid Ambarki, Carsten Wikkelsø, Anders Eklund, Kaj Blennow, Henrik Zetterberg, Mats Tullberg
BACKGROUND: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28505969/early-detection-of-learning-difficulties-when-confronted-with-novel-information-in-preclinical-alzheimer-s-disease-stage-1
#13
Adrià Tort-Merino, Natalia Valech, Claudia Peñaloza, Petra Grönholm-Nyman, María León, Jaume Olives, Ainara Estanga, Mirian Ecay, Juan Fortea, Pablo Martínez-Lage, Jose L Molinuevo, Matti Laine, Antoni Rodríguez-Fornells, Lorena Rami
We employed a highly demanding experimental associative learning test (the AFE-T) to explore memory functioning in Preclinical Alzheimer's Disease stage 1 (PreAD-1) and stage 2 (PreAD-2). The task consisted in the learning of unknown object/name pairs and our comprehensive setup allowed the analysis of learning curves, immediate recall, long-term forgetting rates at one week, three months, and six months, and relearning curves. Forty-nine cognitively healthy subjects were included and classified according to the presence or absence of abnormal CSF biomarkers (Control, n = 31; PreAD-1, n = 14; PreAD-2, n = 4)...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28501451/habitual-exercise-levels-are-associated-with-cerebral-amyloid-load-in-presymptomatic-autosomal-dominant-alzheimer-s-disease
#14
Belinda M Brown, Hamid R Sohrabi, Kevin Taddei, Samantha L Gardener, Stephanie R Rainey-Smith, Jeremiah J Peiffer, Chengjie Xiong, Anne M Fagan, Tammie Benzinger, Virginia Buckles, Kirk I Erickson, Roger Clarnette, Tejal Shah, Colin L Masters, Michael Weiner, Nigel Cairns, Martin Rossor, Neill R Graff-Radford, Stephen Salloway, Jonathan Vöglein, Christoph Laske, James Noble, Peter R Schofield, Randall J Bateman, John C Morris, Ralph N Martins
INTRODUCTION: The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers. METHODS: In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ42, and CSF tau levels was evaluated using linear regression...
May 11, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28498801/extracellular-truncated-tau-causes-early-presynaptic-dysfunction-associated-with-alzheimer-s-disease-and-other-tauopathies
#15
Fulvio Florenzano, Corsetti Veronica, Gabriele Ciasca, Maria Teresa Ciotti, Anna Pittaluga, Gunedalina Olivero, Marco Feligioni, Filomena Iannuzzi, Valentina Latina, Michele Francesco Maria Sciacca, Alessandro Sinopoli, Danilo Milardi, Giuseppe Pappalardo, Marco De Spirito, Massimiliano Papi, Anna Atlante, Antonella Bobba, Antonella Borreca, Pietro Calissano, Giuseppina Amadoro
The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting potential extracellular role(s) of NH2-derived fragments of protein on synaptic dysfunction underlying neurodegenerative tauopathies, including Alzheimer's disease (AD). Here we show that sub-toxic doses of extracellular-applied human NH2tau 26-44 (aka NH2htau) -which is the minimal active moiety of neurotoxic 20-22kDa peptide accumulating in vivo at AD synapses and secreted into parenchyma- acutely provokes presynaptic deficit in K+-evoked glutamate release on hippocampal synaptosomes along with alteration in local Ca2+ dynamics...
April 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28497179/detectable-neuropsychological-differences-in-early-preclinical-alzheimer-s-disease-a-meta-analysis
#16
REVIEW
S Duke Han, Caroline P Nguyen, Nikki H Stricker, Daniel A Nation
The development of methods for in vivo detection of cerebral beta amyloid retention and tau accumulation have been increasingly useful in characterizing preclinical Alzheimer's disease (AD). While the association between these biomarkers and eventual AD has been demonstrated among cognitively intact older adults, the link between biomarkers and neurocognitive ability remains unclear. We conducted a meta-analysis to test the hypothesis that cognitively intact older adults would show statistically discernable differences in neuropsychological performance by amyloid status (amyloid negative = A-, amyloid positive = A+)...
May 11, 2017: Neuropsychology Review
https://www.readbyqxmd.com/read/28487650/neuropsychological-testing-and-machine-learning-distinguish-alzheimer-s-disease-from-other-causes-for-cognitive-impairment
#17
Pavel Gurevich, Hannes Stuke, Andreas Kastrup, Heiner Stuke, Helmut Hildebrandt
With promising results in recent treatment trials for Alzheimer's disease (AD), it becomes increasingly important to distinguish AD at early stages from other causes for cognitive impairment. However, existing diagnostic methods are either invasive (lumbar punctures, PET) or inaccurate Magnetic Resonance Imaging (MRI). This study investigates the potential of neuropsychological testing (NPT) to specifically identify those patients with possible AD among a sample of 158 patients with Mild Cognitive Impairment (MCI) or dementia for various causes...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28486988/cerebrospinal-fluid-a%C3%AE-42-t-tau-and-p-tau-levels-in-the-differential-diagnosis-of-idiopathic-normal-pressure-hydrocephalus-a-systematic-review-and-meta-analysis
#18
REVIEW
Zhongyun Chen, Chunyan Liu, Jie Zhang, Norman Relkin, Yan Xing, Yanfeng Li
OBJECTIVES: The purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagnostic biomarkers for idiopathic normal-pressure hydrocephalus (iNPH) and to assess their utility indistinguishing patients with iNPH from those with Alzheimer disease (AD) and healthy normal controls. METHODS: Studies were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database, VIP Chinese database, and Chinese Bio-medicine Database (CBM) before August 2016...
May 10, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28486088/the-soluble-transcobalamin-receptor-scd320-in-relation-to-alzheimer-s-disease-and-cognitive-scores
#19
Omar Abuyaman, Marc Combrinck, A David Smith, Ebba Nexo
The soluble transcobalamin receptor (sCD320) is present in cerebrospinal fluid and correlates with the dementia-related biomarkers phospho-tau and total-tau. Here we present data on the relation of sCD320 to Alzheimer's disease and scores of cognitive tests. Lumbar cerebrospinal fluid samples from 42 pathologically-confirmed cases of Alzheimer's disease and 25 non-demented controls were analyzed for sCD320 employing an in-house ELISA. The participants' cognitive functions were tested using the Cambridge Cognition Examination (CAMCOG) and the Mini-Mental State Examination (MMSE)...
May 9, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28482211/neuropsychological-measures-that-detect-early-impairment-and-decline-in-preclinical-alzheimer-disease
#20
Suzanne E Schindler, Mateusz S Jasielec, Hua Weng, Jason J Hassenstab, Ellen Grober, Lena M McCue, John C Morris, David M Holtzman, Chengjie Xiong, Anne M Fagan
Identifying which neuropsychological measures detect early cognitive changes associated with Alzheimer disease (AD), brain pathology would be helpful clinically for the diagnosis of early AD and for the design of clinical trials. We evaluated which neuropsychological measures in our cognitive battery are most strongly associated with cerebrospinal fluid (CSF) biomarkers of AD brain pathology. We studied a large cohort (n = 233) of middle-to older-aged community-dwelling individuals (mean age 61 years) who had no clinical symptoms of dementia and underwent baseline CSF collection at baseline...
April 14, 2017: Neurobiology of Aging
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