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Alzheimer's Research & Therapy

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https://www.readbyqxmd.com/read/28709449/a-novel-alzheimer-s-disease-drug-candidate-targeting-inflammation-and-fatty-acid-metabolism
#1
Daniel Daugherty, Joshua Goldberg, Wolfgang Fischer, Richard Dargusch, Pamela Maher, David Schubert
BACKGROUND: CAD-31 is an Alzheimer's disease (AD) drug candidate that was selected on the basis of its ability to stimulate the replication of human embryonic stem cell-derived neural precursor cells as well as in APPswe/PS1ΔE9 AD mice. To move CAD-31 toward the clinic, experiments were undertaken to determine its neuroprotective and pharmacological properties, as well as to assay its therapeutic efficacy in a rigorous mouse model of AD. RESULTS: CAD-31 has potent neuroprotective properties in six distinct nerve cell assays that mimic toxicities observed in the old brain...
July 14, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28709448/no-added-diagnostic-value-of-non-phosphorylated-tau-fraction-p-taurel-in-csf-as-a-biomarker-for-differential-dementia-diagnosis
#2
Joery Goossens, Maria Bjerke, Hanne Struyfs, Ellis Niemantsverdriet, Charisse Somers, Tobi Van den Bossche, Sara Van Mossevelde, Bart De Vil, Anne Sieben, Jean-Jacques Martin, Patrick Cras, Johan Goeman, Peter Paul De Deyn, Christine Van Broeckhoven, Julie van der Zee, Sebastiaan Engelborghs
BACKGROUND: The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ1-42, t-tau, and p-tau181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-taurel), may improve differential dementia diagnosis. The goal of this study is to investigate if p-taurel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. METHODS: The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls...
July 14, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28673336/cerebrospinal-fluid-biomarkers-for-alzheimer-s-and-vascular-disease-vary-by-age-gender-and-apoe-genotype-in-cognitively-normal-adults
#3
Ge Li, Jane B Shofer, Eric C Petrie, Chang-En Yu, Charles W Wilkinson, Dianne P Figlewicz, Andrew Shutes-David, Jing Zhang, Thomas J Montine, Murray A Raskind, Joseph F Quinn, Douglas R Galasko, Elaine R Peskind
BACKGROUND: This study sought to evaluate gender and APOE genotype-related differences in the concentrations of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and cerebrovascular injury across the life span of cognitively normal adults. METHODS: CSF amyloid beta1-42 (Aβ42), phospho-tau-181 (p-tau181), and total tau were measured in 331 participants who were between the ages of 21 and 100. CSF E-selectin and vascular cell adhesion protein 1 (VCAM1) were measured in 249 participants who were between the ages of 50 and 100...
July 3, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28655351/digitally-translated-self-administered-gerocognitive-examination-esage-relationship-with-its-validated-paper-version-neuropsychological-evaluations-and-clinical-assessments
#4
Douglas W Scharre, Shu Ing Chang, Haikady N Nagaraja, Nicole E Vrettos, Robert A Bornstein
BACKGROUND: The original paper Self-Administered Gerocognitive Examination (SAGE) is a valid and reliable cognitive assessment tool used to identify individuals with mild cognitive impairment (MCI) or early dementia. We evaluated identical test questions in a digital format (eSAGE) made for tablet use with the goals of calibrating it against SAGE and establishing its association with other neuropsychological tests and clinical assessments of cognitive impairment. METHODS: Subjects aged 50 and over who had taken SAGE were recruited from community and clinic settings...
June 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28655349/oligomeric-tau-targeted-immunotherapy-in-tg4510-mice
#5
Sulana Schroeder, Aurelie Joly-Amado, Ahlam Soliman, Urmi Sengupta, Rakiz Kayed, Marcia N Gordon, David Morgan
BACKGROUND: Finding ways to reverse or prevent the consequences of pathogenic tau in the brain is of considerable importance for treatment of Alzheimer's disease and other tauopathies. Immunotherapy against tau has shown promise in several mouse models. In particular, an antibody with selectivity for oligomeric forms of tau, tau oligomer monoclonal antibody (TOMA), has shown rescue of the behavioral phenotype in several murine models of tau deposition. METHODS: In this study, we examined the capacity of TOMA to rescue the behavioral, histological, and neurochemical consequences of tau deposition in the aggressive Tg4510 model...
June 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28655344/prevention-of-dendritic-and-synaptic-deficits-and-cognitive-impairment-with-a-neurotrophic-compound
#6
Narjes Baazaoui, Khalid Iqbal
BACKGROUND: The use of neurotrophic factors to treat Alzheimer's disease (AD) is hindered by their blood-brain barrier impermeability, short half-life, and severe side effects. Peptide 021 (P021) is a neurotrophic/neurogenic tetra-peptide that was derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. Admantylated glycine was added to its C-terminal to increase its blood-brain barrier permeability and decrease its degradation by exopeptidases to make it druggable...
June 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28655337/long-term-cognitive-outcome-of-alzheimer-s-disease-and-dementia-with-lewy-bodies-dual-disease-is-worse
#7
Frédéric Blanc, Rachid Mahmoudi, Thérèse Jonveaux, Jean Galmiche, Gilles Chopard, Benjamin Cretin, Catherine Demuynck, Catherine Martin-Hunyadi, Nathalie Philippi, François Sellal, Jean-Marc Michel, Gregory Tio, Melanie Stackfleth, Pierre Vandel, Eloi Magnin, Jean-Luc Novella, Georges Kaltenbach, Athanase Benetos, Erik A Sauleau
BACKGROUND: Longitudinal studies of dementia with Lewy bodies (DLB) are rare. Clinically, DLB is usually considered to worsen into Alzheimer's disease (AD). The aim of our study was to compare the rate of the cognitive decline in DLB, AD, and the association of the two diseases (AD + DLB). METHODS: Using the Regional Network for Diagnostic Aid and Management of Patients with Cognitive Impairment database, which includes all the patients seen at all memory clinics (medical consultation and day hospitals) in four French regions, and beta regression, we compared the longitudinal the Mini-Mental State Examination scores of 1159 patients with AD (n = 1000), DLB (n = 131) and AD + DLB (association of the two) (n = 28) during follow-up of at least 4 years...
June 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#8
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/28610595/stem-cell-models-of-alzheimer-s-disease-progress-and-challenges
#9
REVIEW
Charles Arber, Christopher Lovejoy, Selina Wray
A major challenge to our understanding of the molecular mechanisms of Alzheimer's disease (AD) has been the lack of physiologically relevant in vitro models which capture the precise patient genome, in the cell type of interest, with physiological expression levels of the gene(s) of interest. Induced pluripotent stem cell (iPSC) technology, together with advances in 2D and 3D neuronal differentiation, offers a unique opportunity to overcome this challenge and generate a limitless supply of human neurons for in vitro studies...
June 13, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28592267/a-vaccine-with-a%C3%AE-oligomer-specific-mimotope-attenuates-cognitive-deficits-and-brain-pathologies-in-transgenic-mice-with-alzheimer-s-disease
#10
Shao-Wei Wang, Dong-Qun Liu, Ling-Xiao Zhang, Mei Ji, Yang-Xin Zhang, Quan-Xiu Dong, Shu-Ying Liu, Xi-Xiu Xie, Rui-Tian Liu
BACKGROUND: β-Amyloid peptide (Aβ) oligomers are initial factors used to induce Alzheimer's disease (AD) development, and Aβ monomers have normal physiological function. The antibodies or vaccines against Aβ monomers have serious problems, such as side effects and low curative effects. Therefore, it is essential to specifically target Aβ oligomers rather than monomers for the treatment of AD. METHODS: The mimotopes of Aβ oligomers were obtained by panning the phage-displayed random peptide libraries using oligomer-specific antibodies as targets and expressed on the surface of EBY100 Saccharomyces cerevisiae to generate yeast cell base vaccines...
June 7, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28587660/recommendations-for-cerebrospinal-fluid-collection-for-the-analysis-by-elisa-of-neurogranin-trunc-p75-%C3%AE-synuclein-and-total-tau-in-combination-with-a%C3%AE-1-42-a%C3%AE-1-40
#11
Hugo Vanderstichele, Leentje Demeyer, Shorena Janelidze, Els Coart, Erik Stoops, Kimberley Mauroo, Victor Herbst, Cindy François, Oskar Hansson
BACKGROUND: The pathophysiology of neurodegeneration is complex. Its diagnosis requires an early identification of sequential changes in several hallmarks in the brains of affected subjects. The presence of brain pathology can be visualized in the cerebrospinal fluid (CSF) by protein profiling. It is clear that the field of Alzheimer's disease (AD) will benefit from an integration of algorithms including CSF concentrations of individual proteins, especially as an aid in clinical decision-making or to improve patient enrolment in clinical trials...
June 6, 2017: Alzheimer's Research & Therapy
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
#12
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/28587629/efficacy-of-the-ubiquitous-spaced-retrieval-based-memory-advancement-and-rehabilitation-training-usmart-program-among-patients-with-mild-cognitive-impairment-a-randomized-controlled-crossover-trial
#13
Ji Won Han, Kyung Lak Son, Hye Jin Byun, Ji Won Ko, Kayoung Kim, Jong Woo Hong, Tae Hyun Kim, Ki Woong Kim
BACKGROUND: Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial...
June 6, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28569205/association-between-blood-pressure-and-alzheimer-disease-measured-up-to-27%C3%A2-years-prior-to-diagnosis-the-hunt-study
#14
Jessica Mira Gabin, Kristian Tambs, Ingvild Saltvedt, Erik Sund, Jostein Holmen
BACKGROUND: A lot of attention has been paid to the relationship of blood pressure and dementia because epidemiological research has reported conflicting evidence. Observational data has shown that midlife hypertension is a risk factor for cognitive decline and dementia later in life, whereas there is evidence that low blood pressure is predictive in later life. The aim of the present study was to examine the association between dementia and blood pressure measured up to 27 years (mean 17...
May 31, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28535785/optimizing-medication-appropriateness-in-older-adults-a-randomized-clinical-interventional-trial-to-decrease-anticholinergic-burden
#15
Daniela C Moga, Erin L Abner, Dorinda N Rigsby, Lynne Eckmann, Mark Huffmyer, Richard R Murphy, Beth B Coy, Gregory A Jicha
BACKGROUND: The complexity of medication therapy in older adults with multiple comorbidities often leads to inappropriate prescribing. Drugs with anticholinergic properties are of particular interest because many are not recognized for this property; their use may lead to increased anticholinergic burden resulting in significant health risks, as well as negatively impacting cognition. Medication therapy management (MTM) interventions showed promise in addressing inappropriate medication use, but the effectiveness of targeted multidisciplinary team interventions addressing anticholinergic medications in older populations is yet to be determined...
May 23, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28472970/communicating-mild-cognitive-impairment-diagnoses-with-and-without-amyloid-imaging
#16
REVIEW
Joshua D Grill, Liana G Apostolova, Szofia Bullain, Jeffrey M Burns, Chelsea G Cox, Malcolm Dick, Dean Hartley, Claudia Kawas, Sarah Kremen, Jennifer Lingler, Oscar L Lopez, Mark Mapstone, Aimee Pierce, Gil Rabinovici, J Scott Roberts, Seyed Ahmad Sajjadi, Edmond Teng, Jason Karlawish
BACKGROUND: Mild cognitive impairment (MCI) has an uncertain etiology and prognosis and may be challenging for clinicians to discuss with patients and families. Amyloid imaging may aid specialists in determining MCI etiology and prognosis, but creates novel challenges related to disease labeling. METHODS: We convened a workgroup to formulate recommendations for clinicians providing care to MCI patients. RESULTS: Clinicians should use the MCI diagnosis to validate patient and family concerns and educate them that the patient's cognitive impairment is not normal for his or her age and education level...
May 4, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28446202/analyzing-the-genes-related-to-alzheimer-s-disease-via-a-network-and-pathway-based-approach
#17
Yan-Shi Hu, Juncai Xin, Ying Hu, Lei Zhang, Ju Wang
BACKGROUND: Our understanding of the molecular mechanisms underlying Alzheimer's disease (AD) remains incomplete. Previous studies have revealed that genetic factors provide a significant contribution to the pathogenesis and development of AD. In the past years, numerous genes implicated in this disease have been identified via genetic association studies on candidate genes or at the genome-wide level. However, in many cases, the roles of these genes and their interactions in AD are still unclear...
April 27, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28446209/antipsychotic-prescribing-for-alzheimer-s-disease-and-related-disorders-in-specialized-settings-from-2010-to-2014-in-france-a-repeated-cross-sectional-study
#18
Karim Tifratene, Valeria Manera, Roxane Fabre, Auriane Gros, Susanne Thummler, Christian Pradier, Philippe Robert, Renaud David
BACKGROUND: Safety warnings from health authorities are currently intended to limit the use of antipsychotics (APs) in dementia-related conditions to treat neuropsychiatric symptoms, such as disturbing and/or delusional behaviors. The aim of this study is to investigate prevalence, correlates and trends of AP prescribing among people with dementia between 2010 and 2014 in the French population. METHODS: AP prescribing and associated factors among individuals with AD, mixed dementia and vascular dementia in the French National Alzheimer Database between 2010 and 2014 were analyzed using multivariate generalized estimating equations models (n = 199,549)...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28446207/memory-is-preserved-in-older-adults-taking-at1-receptor-blockers
#19
Jean K Ho, Daniel A Nation
BACKGROUND: Prior work suggests that some but not all antihypertensive treatments may benefit cognition and risk for Alzheimer's disease, independent of stroke. Angiotensin II receptor blockers (ARBs) have been highlighted as one antihypertensive drug class that may confer greatest benefit. METHODS: The participants comprised 1626 nondemented adults, aged 55-91 years, recruited from Alzheimer's Disease Neuroimaging Initiative sites. Three groups were compared: ARB users (HTN-ARBs), other antihypertensive drug users (HTN-Other), and normotensives...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28441967/comparison-of-csf-markers-and-semi-quantitative-amyloid-pet-in-alzheimer-s-disease-diagnosis-and-in-cognitive-impairment-prognosis-using-the-adni-2-database
#20
Fayçal Ben Bouallègue, Denis Mariano-Goulart, Pierre Payoux
BACKGROUND: The relative performance of semi-quantitative amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) markers in diagnosing Alzheimer's disease (AD) and predicting the cognitive evolution of patients with mild cognitive impairment (MCI) is still debated. METHODS: Subjects from the Alzheimer's Disease Neuroimaging Initiative 2 with complete baseline cognitive assessment (Mini Mental State Examination, Clinical Dementia Rating [CDR] and Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-cog] scores), CSF collection (amyloid-β1-42 [Aβ], tau and phosphorylated tau) and (18)F-florbetapir scans were included in our cross-sectional cohort...
April 26, 2017: Alzheimer's Research & Therapy
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