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Alzheimer's Research & Therapy

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28851451/structured-physical-exercise-improves-neuropsychiatric-symptoms-in-acute-dementia-care-a-hospital-based-rct
#11
Tim Fleiner, Hannah Dauth, Marleen Gersie, Wiebren Zijlstra, Peter Haussermann
BACKGROUND: The primary objective of this trial is to investigate the effects of a short-term exercise program on neuropsychiatric signs and symptoms in acute hospital dementia care. METHODS: Within a hospital-based randomized controlled trial, the intervention group conducted a 2-week exercise program with four 20-min exercise sessions on 3 days per week. The control group conducted a social stimulation program. Effects on neuropsychiatric signs and symptoms were measured via the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change, the Neuropsychiatric Inventory, and the Cohen-Mansfield Agitation Inventory...
August 29, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28851448/dietary-arachidonic-acid-increases-deleterious-effects-of-amyloid-%C3%AE-oligomers-on-learning-abilities-and-expression-of-ampa-receptors-putative-role-of-the-acsl4-cpla2-balance
#12
Mélanie H Thomas, Cédric Paris, Mylène Magnien, Julie Colin, Sandra Pelleïeux, Florence Coste, Marie-Christine Escanyé, Thierry Pillot, Jean-Luc Olivier
BACKGROUND: Polyunsaturated fatty acids play a crucial role in neuronal function, and the modification of these compounds in the brain could have an impact on neurodegenerative diseases such as Alzheimer's disease. Despite the fact that arachidonic acid is the second foremost polyunsaturated fatty acid besides docosahexaenoic acid, its role and the regulation of its transfer and mobilization in the brain are poorly known. METHODS: Two groups of 39 adult male BALB/c mice were fed with an arachidonic acid-enriched diet or an oleic acid-enriched diet, respectively, for 12 weeks...
August 29, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28851447/cognitive-and-imaging-markers-in-non-demented-subjects-attending-a-memory-clinic-study-design-and-baseline-findings-of-the-memento-cohort
#13
Carole Dufouil, Bruno Dubois, Bruno Vellas, Florence Pasquier, Frédéric Blanc, Jacques Hugon, Olivier Hanon, Jean-François Dartigues, Sandrine Harston, Audrey Gabelle, Mathieu Ceccaldi, Olivier Beauchet, Pierre Krolak-Salmon, Renaud David, Olivier Rouaud, Olivier Godefroy, Catherine Belin, Isabelle Rouch, Nicolas Auguste, David Wallon, Athanase Benetos, Jérémie Pariente, Marc Paccalin, Olivier Moreaud, Caroline Hommet, François Sellal, Claire Boutoleau-Bretonniére, Isabelle Jalenques, Armelle Gentric, Pierre Vandel, Chabha Azouani, Ludovic Fillon, Clara Fischer, Helen Savarieau, Gregory Operto, Hugo Bertin, Marie Chupin, Vincent Bouteloup, Marie-Odile Habert, Jean-François Mangin, Geneviève Chêne
BACKGROUND: The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. METHODS: In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1...
August 29, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28830516/cost-of-diagnosing-dementia-in-a-german-memory-clinic
#14
Bernhard Michalowsky, Steffen Flessa, Johannes Hertel, Olav Goetz, Wolfgang Hoffmann, Stefan Teipel, Ingo Kilimann
BACKGROUND: Little is known about diagnostic work-ups or the costs of diagnosing dementia in specialized care. Here, we analyzed the costs of diagnosing dementia according to specific dementia disorders. METHODS: A prospective descriptive design was used to analyze the cost of diagnosing dementia for 120 patients with suspected dementia at a German memory clinic. The duration of clinical consultations and use of technical procedures were recorded by the memory clinic staff...
August 22, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28830506/a-coiled-conformation-of-amyloid-%C3%AE-recognized-by-antibody-c706
#15
Alexey Teplyakov, Galina Obmolova, Gary L Gilliland
BACKGROUND: β-Amyloid (Aβ) peptide is believed to play a pivotal role in the development of Alzheimer's disease. Passive immunization with anti-Aβ monoclonal antibodies may facilitate the clearance of Aβ in the brain and may thus prevent the downstream pathology. Antibodies targeting the immunodominant N-terminal epitope of Aβ and capable of binding both the plaques and soluble species have been most efficacious in animal models. Structural studies of such antibodies with bound Aβ peptides provided the basis for understanding the mechanisms of action and the differences in potency...
August 22, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28818116/distinct-white-matter-microstructural-abnormalities-and-extracellular-water-increases-relate-to-cognitive-impairment-in-alzheimer-s-disease-with-and-without-cerebrovascular-disease
#16
Fang Ji, Ofer Pasternak, Siwei Liu, Yng Miin Loke, Boon Linn Choo, Saima Hilal, Xin Xu, Mohammad Kamran Ikram, Narayanaswamy Venketasubramanian, Christopher Li-Hsian Chen, Juan Zhou
BACKGROUND: Mixed vascular and neurodegenerative dementia, such as Alzheimer's disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28818092/associations-of-thyroid-hormone-serum-levels-with-in-vivo-alzheimer-s-disease-pathologies
#17
Hyo Jung Choi, Min Soo Byun, Dahyun Yi, Bo Kyung Sohn, Jun Ho Lee, Jun-Young Lee, Yu Kyung Kim, Dong Young Lee
BACKGROUND: The present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer's disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals. METHODS: This study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included (11)C-Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, (18)F-deoxyglucose (FDG)-PET scans, and the quantification of serum triiodothyronine (T3), free T3, free thyroxine (fT4), and TSH levels...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28818091/non-canonical-soluble-amyloid-beta-aggregates-and-plaque-buffering-controversies-and-future-directions-for-target-discovery-in-alzheimer-s-disease
#18
REVIEW
David L Brody, Hao Jiang, Norelle Wildburger, Thomas J Esparza
The specific amyloid-beta (Aβ) species or other amyloid-precursor protein cleavage products that are most directly related to human neurodegeneration and clinical dementia of the Alzheimer's type have not yet been directly identified. Without a clear understanding of the most relevant species, it is difficult to determine whether therapeutic candidates successfully engaged the correct target(s). Here, we review some of the controversies regarding soluble Aβ aggregates (also termed oligomers, dimers, trimers, Aβ*56, amylospheroids, etc...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28793933/can-cognitive-assessment-really-discriminate-early-stages-of-alzheimer-s-and-behavioural-variant-frontotemporal-dementia-at-initial-clinical-presentation
#19
Sophia Reul, Hubertus Lohmann, Heinz Wiendl, Thomas Duning, Andreas Johnen
BACKGROUND: Neuropsychological testing is considered crucial for differential diagnosis of Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD). In-depth neuropsychological assessment revealed specific dysfunctions in the two dementia syndromes. However, a significant overlap of cognitive impairments exists in early disease stages. We questioned whether a standard neuropsychological assessment at initial clinical presentation can delineate patients with AD versus bvFTD...
August 9, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28793924/on-the-path-to-2025-understanding-the-alzheimer-s-disease-continuum
#20
REVIEW
Paul S Aisen, Jeffrey Cummings, Clifford R Jack, John C Morris, Reisa Sperling, Lutz Frölich, Roy W Jones, Sherie A Dowsett, Brandy R Matthews, Joel Raskin, Philip Scheltens, Bruno Dubois
Basic research advances in recent years have furthered our understanding of the natural history of Alzheimer's disease (AD). It is now recognized that pathophysiological changes begin many years prior to clinical manifestations of disease and the spectrum of AD spans from clinically asymptomatic to severely impaired. Defining AD purely by its clinical presentation is thus artificial and efforts have been made to recognize the disease based on both clinical and biomarker findings. Advances with biomarkers have also prompted a shift in how the disease is considered as a clinico-pathophysiological entity, with an increasing appreciation that AD should not only be viewed with discrete and defined clinical stages, but as a multifaceted process moving along a seamless continuum...
August 9, 2017: Alzheimer's Research & Therapy
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