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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/29121998/circulating-brain-enriched-micrornas-as-novel-biomarkers-for-detection-and-differentiation-of-neurodegenerative-diseases
#1
Kira S Sheinerman, Jon B Toledo, Vladimir G Tsivinsky, David Irwin, Murray Grossman, Daniel Weintraub, Howard I Hurtig, Alice Chen-Plotkin, David A Wolk, Leo F McCluskey, Lauren B Elman, John Q Trojanowski, Samuil R Umansky
BACKGROUND: Minimally invasive specific biomarkers of neurodegenerative diseases (NDs) would facilitate patient selection and disease progression monitoring. We describe the assessment of circulating brain-enriched microRNAs as potential biomarkers for Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). METHODS: In this case-control study, the plasma samples were collected from 250 research participants with a clinical diagnosis of AD, FTD, PD, and ALS, as well as from age- and sex-matched control subjects (n = 50 for each group), recruited from 2003 to 2015 at the University of Pennsylvania Health System, including the Alzheimer's Disease Center, the Parkinson's Disease and Movement Disorders Center, the Frontotemporal Degeneration Center, and the Amyotrophic Lateral Sclerosis Clinic...
November 9, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29096697/race-modifies-the-relationship-between-cognition-and-alzheimer-s-disease-cerebrospinal-fluid-biomarkers
#2
Jennifer C Howell, Kelly D Watts, Monica W Parker, Junjie Wu, Alexander Kollhoff, Thomas S Wingo, Cornelya D Dorbin, Deqiang Qiu, William T Hu
BACKGROUND: African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD...
November 2, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29070066/the-edinburgh-consensus-preparing-for-the-advent-of-disease-modifying-therapies-for-alzheimer-s-disease
#3
LETTER
Craig W Ritchie, Tom C Russ, Sube Banerjee, Bob Barber, Andrew Boaden, Nick C Fox, Clive Holmes, Jeremy D Isaacs, Ira Leroi, Simon Lovestone, Matt Norton, John O'Brien, Jim Pearson, Richard Perry, James Pickett, Adam D Waldman, Wai Lup Wong, Martin N Rossor, Alistair Burns
CONTEXT: This commentary discusses the implications of disease-modifying treatments for Alzheimer's disease which seem likely to appear in the next few years and results from a meeting of British experts in neurodegenerative diseases in Edinburgh. The availability of such treatments would help change public and professional attitudes and accelerate engagement with the prodromal and preclinical populations who might benefit from them. However, this would require an updated understanding of Alzheimer's disease, namely the important distinction between Alzheimer's disease and Alzheimer's dementia...
October 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29061195/preclinical-effects-of-apoe-%C3%AE%C2%B54-on-cerebrospinal-fluid-a%C3%AE-42-concentrations
#4
Ronald Lautner, Philip S Insel, Tobias Skillbäck, Bob Olsson, Mikael Landén, Giovanni B Frisoni, Sanna-Kaisa Herukka, Harald Hampel, Anders Wallin, Lennart Minthon, Oskar Hansson, Kaj Blennow, Niklas Mattsson, Henrik Zetterberg
BACKGROUND: From earlier studies it is known that the APOE ε2/ε3/ε4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid1-42 (Aβ42) in patients with cognitive decline due to Alzheimer's disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF Aβ42 varies by age, to understand the association between APOE and the onset of preclinical AD...
October 23, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29041968/dynamic-changes-of-oligomeric-amyloid-%C3%AE-levels-in-plasma-induced-by-spiked-synthetic-a%C3%AE-42
#5
Seong Soo A An, Byoung-Sub Lee, Ji Sun Yu, Kuntaek Lim, Gwang Je Kim, Ryan Lee, Shinwon Kim, Sungmin Kang, Young Ho Park, Min Jeong Wang, Young Soon Yang, Young Chul Youn, SangYun Kim
BACKGROUND: A reliable blood-based assay is required to properly diagnose and monitor Alzheimer's disease (AD). Many attempts have been made to develop such a diagnostic tool by measuring amyloid-β oligomers (AβOs) in the blood, but none have been successful in terms of method reliability. We present a multimer detection system (MDS), initially developed for the detection of prion oligomers in the blood, to detect AβOs. METHODS: To characterize Aβ in the blood, plasma was spiked with synthetic amyloid-β (Aβ) and incubated over time...
October 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29017593/incremental-value-of-biomarker-combinations-to-predict-progression-of-mild-cognitive-impairment-to-alzheimer-s-dementia
#6
Lutz Frölich, Oliver Peters, Piotr Lewczuk, Oliver Gruber, Stefan J Teipel, Hermann J Gertz, Holger Jahn, Frank Jessen, Alexander Kurz, Christian Luckhaus, Michael Hüll, Johannes Pantel, Friedel M Reischies, Johannes Schröder, Michael Wagner, Otto Rienhoff, Stefanie Wolf, Chris Bauer, Johannes Schuchhardt, Isabella Heuser, Eckart Rüther, Fritz Henn, Wolfgang Maier, Jens Wiltfang, Johannes Kornhuber
BACKGROUND: The progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia can be predicted by cognitive, neuroimaging, and cerebrospinal fluid (CSF) markers. Since most biomarkers reveal complementary information, a combination of biomarkers may increase the predictive power. We investigated which combination of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)-sum-of-boxes, the word list delayed free recall from the Consortium to Establish a Registry of Dementia (CERAD) test battery, hippocampal volume (HCV), amyloid-beta1-42 (Aβ42), amyloid-beta1-40 (Aβ40) levels, the ratio of Aβ42/Aβ40, phosphorylated tau, and total tau (t-Tau) levels in the CSF best predicted a short-term conversion from MCI to AD dementia...
October 10, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28982376/gene-suppression-approaches-to-neurodegeneration
#7
REVIEW
Rhia Ghosh, Sarah J Tabrizi
Gene suppression approaches have emerged over the last 20 years as a novel therapeutic approach for the treatment of neurodegenerative diseases. These include RNA interference and anti-sense oligonucleotides, both of which act at the post-transcriptional level, and genome-editing techniques, which aim to repair the responsible mutant gene. All serve to inhibit the expression of disease-causing proteins, leading to the potential prevention or even reversal of the disease phenotype. In this review we summarise the main developments in gene suppression strategies, using examples from Huntington's disease and other inherited causes of neurodegeneration, and explore how these might illuminate a path to tackle other proteinopathy-associated dementias in the future...
October 5, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28982375/pkr-involvement-in-alzheimer-s-disease
#8
REVIEW
Jacques Hugon, François Mouton-Liger, Julien Dumurgier, Claire Paquet
BACKGROUND: Brain lesions in Alzheimer's disease (AD) are characterized by Aβ accumulation, neurofibrillary tangles, and synaptic and neuronal vanishing. According to the amyloid cascade hypothesis, Aβ1-42 oligomers could trigger a neurotoxic cascade with kinase activation that leads to tau phosphorylation and neurodegeneration. Detrimental pathways that are associated with kinase activation could also be linked to the triggering of direct neuronal death, the production of free radicals, and neuroinflammation...
October 5, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28978359/n-truncated-a%C3%AE-4-x-peptides-in-sporadic-alzheimer-s-disease-cases-and-transgenic-alzheimer-mouse-models
#9
Oliver Wirths, Susanne Walter, Inga Kraus, Hans W Klafki, Martina Stazi, Timo J Oberstein, Jorge Ghiso, Jens Wiltfang, Thomas A Bayer, Sascha Weggen
BACKGROUND: The deposition of neurotoxic amyloid-β (Aβ) peptides in plaques in the brain parenchyma and in cerebral blood vessels is considered to be a key event in Alzheimer's disease (AD) pathogenesis. Although the presence and impact of full-length Aβ peptides such as Aβ1-40 and Aβ1-42 have been analyzed extensively, the deposition of N-terminally truncated Aβ peptide species has received much less attention, largely because of the lack of specific antibodies. METHODS: This paper describes the generation and characterization of novel antibodies selective for Aβ4-x peptides and provides immunohistochemical evidence of Aβ4-x in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models...
October 4, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28978335/attitudes-toward-clinical-trials-across-the-alzheimer-s-disease-spectrum
#10
Michelle M Nuño, Daniel L Gillen, Kulwant K Dosanjh, Jenny Brook, David Elashoff, John M Ringman, Joshua D Grill
BACKGROUND: Research has revealed that manifest Alzheimer's disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms...
October 4, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28934977/er%C3%AE-and-apoe-isoforms-interact-to-regulate-bdnf-5-ht2a-signaling-and-synaptic-function-in-the-female-brain
#11
Anindit Chhibber, Liqin Zhao
BACKGROUND: Depression has been reported to be commonly manifested in patients with Alzheimer's disease (AD) and is considered a risk factor for AD. The human apolipoprotein E (ApoE) gene exists in three major isoforms (coded by ε2, ε3, and ε4), and the ε4 allele has been associated with a greater incidence of both depression and AD. Although mounting evidence points to the potentially complex interaction between these two brain disorders in which ApoE might play a role, the underlying mechanisms are largely unknown...
September 21, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28934963/metabolic-status-of-csf-distinguishes-rats-with-tauopathy-from-controls
#12
Radana Karlíková, Kateřina Mičová, Lukáš Najdekr, Alžběta Gardlo, Tomáš Adam, Petra Majerová, David Friedecký, Andrej Kováč
BACKGROUND: Tauopathies represent heterogeneous groups of neurodegenerative diseases that are characterised by abnormal deposition of the microtubule-associated protein tau. Alzheimer's disease is the most prevalent tauopathy, affecting more than 35 million people worldwide. In this study we investigated changes in metabolic pathways associated with tau-induced neurodegeneration. METHODS: Cerebrospinal fluid (CSF), plasma and brain tissue were collected from a transgenic rat model for tauopathies and from age-matched control animals...
September 21, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28931441/tracking-progressive-pathological-and-functional-decline-in-the-rtg4510-mouse-model-of-tauopathy
#13
Thomas Blackmore, Soraya Meftah, Tracey Karen Murray, Peter James Craig, Anthony Blockeel, Keith Phillips, Brian Eastwood, Michael J O'Neill, Hugh Marston, Zeshan Ahmed, Gary Gilmour, Francois Gastambide
BACKGROUND: The choice and appropriate use of animal models in drug discovery for Alzheimer's disease (AD) is pivotal to successful clinical translation of novel therapeutics, yet true alignment of research is challenging. Current models do not fully recapitulate the human disease, and even exhibit various degrees of regional pathological burden and diverse functional alterations. Given this, relevant pathological and functional endpoints must be determined on a model-by-model basis. The present work explores the rTg4510 mouse model of tauopathy as a case study to define best practices for the selection and validation of cognitive and functional endpoints for the purposes of pre-clinical AD drug discovery...
September 20, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28931428/personalized-predictive-modeling-for-patients-with-alzheimer-s-disease-using-an-extension-of-sullivan-s-life-table-model
#14
Eric Stallard, Bruce Kinosian, Yaakov Stern
BACKGROUND: Alzheimer's disease (AD) progression varies substantially among patients, hindering calculation of residual total life expectancy (TLE) and its decomposition into disability-free life expectancy (DFLE) and disabled life expectancy (DLE) for individual patients with AD. The objective of the present study was to assess the accuracy of a new synthesis of Sullivan's life table (SLT) and longitudinal Grade of Membership (L-GoM) models that estimates individualized TLEs, DFLEs, and DLEs for patients with AD...
September 20, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28931427/serotonin-5-ht6-receptors-affect-cognition-in-a-mouse-model-of-alzheimer-s-disease-by-regulating-cilia-function
#15
Lili Hu, Bingjie Wang, Yan Zhang
BACKGROUND: Serotonin receptor 5-HT6 is involved in cognition and Alzheimer's disease (AD) development. However, the mechanism of 5-HT6 in AD pathology is not clear. METHODS: Since 5-HT6 is almost exclusively expressed in the primary cilia, using immunostaining we examined the number of cilia in the hippocampus of AD animal model APP/PS1 mice. By overexpressing and knocking down 5-HT6 in the primary cultured hippocampal neurons, we investigated the roles of 5-HT6 in alternating ciliary morphology...
September 20, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28899429/amyloid-independent-atrophy-patterns-predict-time-to-progression-to-dementia-in-mild-cognitive-impairment
#16
Mara Ten Kate, Frederik Barkhof, Pieter Jelle Visser, Charlotte E Teunissen, Philip Scheltens, Wiesje M van der Flier, Betty M Tijms
BACKGROUND: Amyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer's disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus...
September 12, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28899422/moderating-effects-of-sex-on-the-impact-of-diagnosis-and-amyloid-positivity-on-verbal-memory-and-hippocampal-volume
#17
Jessica Z K Caldwell, Jody-Lynn Berg, Jeffrey L Cummings, Sarah J Banks
BACKGROUND: Alzheimer's disease (AD) impacts men and women differently, but the effect of sex on predementia stages is unclear. The objective of this study was to examine whether sex moderates the impact of florbetapir positron emission tomography (PET) amyloid positivity (A(+)) on verbal learning and memory performance and hippocampal volume (HV) in normal cognition (NC) and early mild cognitive impairment (eMCI). METHODS: Seven hundred forty-two participants with NC and participants with eMCI from the Alzheimer's Disease Neuroimaging Initiative (second cohort [ADNI2] and Grand Opportunity Cohort [ADNI-GO]) were included...
September 12, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28899417/serotonin-augmentation-therapy-by-escitalopram-has-minimal-effects-on-amyloid-%C3%AE-levels-in-early-stage-alzheimer-s-like-disease-in-mice
#18
Christian Ulrich von Linstow, Jonas Waider, Manuela Grebing, Athanasios Metaxas, Klaus Peter Lesch, Bente Finsen
BACKGROUND: Dysfunction of the serotonergic (5-HTergic) system has been implicated in the cognitive and behavioural symptoms of Alzheimer's disease (AD). Accumulation of toxic amyloid-β (Aβ) species is a hallmark of AD and an instigator of pathology. Serotonin (5-HT) augmentation therapy by treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with AD has had mixed success in improving cognitive function, whereas SSRI administration to mice with AD-like disease has been shown to reduce Aβ pathology...
September 12, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28899416/alzheimer-s-disease-prevention-from-risk-factors-to-early-intervention
#19
REVIEW
Marta Crous-Bou, Carolina Minguillón, Nina Gramunt, José Luis Molinuevo
Due to the progressive aging of the population, Alzheimer's disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild-moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant...
September 12, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28859660/early-versus-late-onset-alzheimer-s-disease-in-clinical-practice-cognitive-and-global-outcomes-over-3%C3%A2-years
#20
Carina Wattmo, Åsa K Wallin
BACKGROUND: Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD) in clinical practice. METHODS: This 3-year, prospective, observational, multicentre study included 1017 participants with mild to moderate AD; 143 had EOAD (age at onset < 65 years) and 874 had LOAD (age at onset ≥ 65 years)...
August 31, 2017: Alzheimer's Research & Therapy
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