99,287 results match your criteria Alzheimer's Research & Therapy [Journal]


Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease.

Neuroimage Clin 2019 Apr 10;23:101823. Epub 2019 Apr 10.

Department of Radiology, Mayo Clinic, Rochester, MN, USA.

The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101823DOI Listing
April 2019
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Protective function of autophagy during VLCFA-induced cytotoxicity in a neurodegenerative cell model.

Free Radic Biol Med 2019 Apr 17. Epub 2019 Apr 17.

Université de Bourgogne Franche-Comté, Dijon, F-21000, France; Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270, Inserm, F-21000, Dijon, France. Electronic address:

In recent years, a particular interest has focused on the accumulation of fatty acids with very long chains (VLCFA) in the occurrence of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis or dementia. Indeed, it seems increasingly clear that this accumulation of VLCFA in the central nervous system is accompanied by a progressive demyelination resulting in death of neuronal cells. Nevertheless, molecular mechanisms by which VLCFA result in toxicity remain unclear. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2019.04.016DOI Listing

Exendin-4 attenuates brain mitochondrial toxicity through PI3K/Akt-dependent pathway in amyloid beta (1-42)-induced cognitive deficit rats.

Neurochem Int 2019 Apr 17. Epub 2019 Apr 17.

Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, 281 406, India.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, disorientation and gradual deterioration of intellectual ability. In the pharmacotherapy of AD, the mitochondrial protective activity of Exendin-4 in experimental studies is yet to be established though its effectiveness is demonstrated in these patients. Therefore, the mitochondria protective activity of Exendin-4 (5 μg/kg, i. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01970186193002
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http://dx.doi.org/10.1016/j.neuint.2019.04.006DOI Listing
April 2019
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Therapeutic Efficacy of Glial Cell-Derived Neurotrophic Factor Loaded Collagen Scaffolds in ex vivo organotypic brain slice Parkinson's Disease Models.

Brain Res Bull 2019 Apr 17. Epub 2019 Apr 17.

Laboratory of Psychiatry and Experimental Alzheimer's Research, Medical University of Innsbruck, Austria. Electronic address:

Glial cell line-derived neurotrophic factor (GDNF) is a potent trophic factor that supports the survival of dopaminergic neurons of the substantia nigra (SN), which degenerate in Parkinson's disease (PD). The application of GDNF to the brain is challenging but biomaterials such as collagen can present novel strategies to target therapeutics to the brain. In this study, we assess the efficacy of collagen scaffolds loaded with GDNF on dopaminergic neuronal survival in organotypic ex vivo slices: axotomy, rotenone, and 6-hydroxydopamine (6-OHDA) models. Read More

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http://dx.doi.org/10.1016/j.brainresbull.2019.04.012DOI Listing
April 2019
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Heparanase protects the heart against chemical or ischemia/reperfusion injury.

J Mol Cell Cardiol 2019 Apr 17. Epub 2019 Apr 17.

Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address:

Although cancer cells use heparanase for tumor metastasis, favourable effects of heparanase have been reported in the management of Alzheimer's disease and diabetes. Indeed, we previously established a protective function for heparanase in the acutely diabetic heart, where it conferred cardiomyocyte resistance to oxidative stress and apoptosis by provoking changes in gene expression. In this study, we tested if overexpression of heparanase can protect the heart against chemically induced or ischemia/reperfusion (I/R) injury. Read More

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http://dx.doi.org/10.1016/j.yjmcc.2019.04.008DOI Listing

LRP1 Has a Predominant Role in Production over Clearance of Aβ in a Mouse Model of Alzheimer's Disease.

Mol Neurobiol 2019 Apr 19. Epub 2019 Apr 19.

Laboratory for Experimental Mouse Genetics, Department of Human Genetics, KU Leuven, Herestraat 49, Box 604, 3000, Leuven, Belgium.

The low-density lipoprotein receptor-related protein-1 (LRP1) has a dual role in the metabolism of the amyloid precursor protein (APP). In cellular models, LRP1 enhances amyloid-β (Aβ) generation via APP internalization and thus its amyloidogenic processing. However, conditional knock-out studies in mice define LRP1 as an important mediator for the clearance of extracellular Aβ from brain via cellular degradation or transcytosis across the blood-brain barrier (BBB). Read More

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http://dx.doi.org/10.1007/s12035-019-1594-2DOI Listing

Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study.

Sci Rep 2019 Apr 19;9(1):6320. Epub 2019 Apr 19.

Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.

Research has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936 (n = 603); and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study (n = 155). Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. Read More

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http://www.nature.com/articles/s41598-019-42534-x
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http://dx.doi.org/10.1038/s41598-019-42534-xDOI Listing
April 2019
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Preparation of Benzothiazolyl-Decorated Nanoliposomes.

Molecules 2019 Apr 18;24(8). Epub 2019 Apr 18.

Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, 26510 Rio, Greece.

Amyloid β (Aβ) species are considered as potential targets for the development of diagnostics/therapeutics towards Alzheimer's disease (AD). Nanoliposomes which are decorated with molecules having high affinity for Aβ species may be considered as potential carriers for AD theragnostics. Herein, benzothiazolyl (BTH) decorated nanoliposomes were prepared for the first time, after synthesis of a lipidic BTH derivative (lipid-BTH). Read More

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http://dx.doi.org/10.3390/molecules24081540DOI Listing

AGE-RELATED DEFICIT ACCUMULATION AND THE DISEASES OF AGEING.

Mech Ageing Dev 2019 Apr 16. Epub 2019 Apr 16.

Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.

With ageing, the potency of individual risk factors traditionally associated with common illnesses declines. Instead, it is becoming clear that the impact of a wide range of age-related deficits not traditionally considered as risk factors for these illnesses increases. These age-related deficits chiefly confer risk as a group, not individually. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00476374193001
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http://dx.doi.org/10.1016/j.mad.2019.04.005DOI Listing
April 2019
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Association of Accelerometer-Measured Light-Intensity Physical Activity With Brain Volume: The Framingham Heart Study.

JAMA Netw Open 2019 Apr 5;2(4):e192745. Epub 2019 Apr 5.

Framingham Heart Study, Framingham, Massachusetts.

Importance: Dementia risk may be attenuated by physical activity (PA); however, the specific activity levels optimal for dementia prevention are unclear. Moreover, most older adults are unable to meet the nationally recommended PA guidelines, set at 150 minutes of moderate to vigorous PA per week.

Objective: To assess the association of total steps walked per day and total dose (intensity × duration) of PA with brain volumes on magnetic resonance imaging (MRI) among Framingham Heart Study participants. Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2019.2745DOI Listing

Aggregation of Microtubule Binding Repeats of Tau Protein is Promoted by Cu.

ACS Omega 2019 Mar 15;4(3):5356-5366. Epub 2019 Mar 15.

Department of Physical and Environmental Science, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4, Canada.

Understanding the factors that give rise to tau aggregation and reactive oxygen species (ROS) is the key aspect in Alzheimer's disease pathogenesis. Microtubule (MT) binding repeats of tau protein were suggested to play a critical role in tau aggregation. Here, we show that the interaction of Cu with full-length MT binding repeats R1-R4 leads to the aggregation, and a Cys-based redox chemistry is critically involved in tau aggregation leading to disulfide-bridge dimerization of R2 and R3 and further aggregation into a fibrillar structure. Read More

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http://pubs.acs.org/doi/10.1021/acsomega.8b03595
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http://dx.doi.org/10.1021/acsomega.8b03595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463671PMC
March 2019
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Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system.

Sci Adv 2019 Apr 17;5(4):eaav1388. Epub 2019 Apr 17.

Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.

Detection of amyloid-β (Aβ) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Aβ is deemed a less invasive and more accessible hallmark of AD, as Aβ can penetrate blood-brain barriers. However, correlations between biofluidic Aβ concentrations and AD progression has been tenuous. Read More

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http://dx.doi.org/10.1126/sciadv.aav1388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469948PMC

Rare Variants Imputation in Admixed Populations: Comparison Across Reference Panels and Bioinformatics Tools.

Front Genet 2019 3;10:239. Epub 2019 Apr 3.

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, United States.

Background: Imputation has become a standard approach in genome-wide association studies (GWAS) to infer untyped markers. Although feasibility for common variants imputation is well established, we aimed to assess rare and ultra-rare variants' imputation in an admixed Caribbean Hispanic population (CH).

Methods: We evaluated imputation accuracy in CH ( = 1,000), focusing on rare (0. Read More

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http://dx.doi.org/10.3389/fgene.2019.00239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456789PMC

Age, but Not Amyloidosis, Induced Changes in Global Levels of Histone Modifications in Susceptible and Disease-Resistant Neurons in Alzheimer's Disease Model Mice.

Front Aging Neurosci 2019 3;11:68. Epub 2019 Apr 3.

Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia.

There is increasing interest in the role of epigenetic alterations in Alzheimer's disease (AD). The epigenome of every cell type is distinct, yet data regarding epigenetic change in specific cell types in aging and AD is limited. We investigated histone tail modifications in neuronal subtypes in wild-type and APP/PS1 mice at 3 (pre-pathology), 6 (pathology-onset) and 12 (pathology-rich) months of age. Read More

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http://dx.doi.org/10.3389/fnagi.2019.00068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456813PMC
April 2019
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Chronic Microglial Activation in the GFAP-IL6 Mouse Contributes to Age-Dependent Cerebellar Volume Loss and Impairment in Motor Function.

Front Neurosci 2019 3;13:303. Epub 2019 Apr 3.

Pharmacology Unit, School of Medicine, Western Sydney University, Penrith, NSW, Australia.

Chronic microglial activation is a prominent feature of many chronic neurodegenerative diseases, including Parkinson's and Alzheimer's disease. To investigate the effects of chronic microglial activation on cerebellar structure and motor function throughout the lifespan, the transgenic GFAP-IL6 mouse model was used. The aim of the study was to examine inflammatory markers and neuronal degeneration while simultaneously characterizing the motor performance of GFAP-IL6 mice at 3, 6, 14, and 24 months of age in comparison to WT (C57BL/6) mice. Read More

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http://dx.doi.org/10.3389/fnins.2019.00303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456818PMC

Gene-Environment-Time Interactions in Neurodegenerative Diseases: Hypotheses and Research Approaches.

Ann Neurosci 2018 Dec 4;25(4):261-267. Epub 2018 Dec 4.

Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.

Background: Amyotrophic lateral sclerosis (ALS), Alzheimer's, and Parkinson's diseases are age-related neurodegenerative diseases. ALS is not a single entity but a syndrome with many different causes. In all 3 diseases, gene mutations account for only 10-15% of cases. Read More

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https://www.karger.com/Article/FullText/495321
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http://dx.doi.org/10.1159/000495321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470336PMC
December 2018
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Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice.

Acta Pharmacol Sin 2019 Apr 18. Epub 2019 Apr 18.

Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of β-amyloid (Aβ) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aβ clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. Read More

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http://dx.doi.org/10.1038/s41401-019-0220-1DOI Listing

Felodipine induces autophagy in mouse brains with pharmacokinetics amenable to repurposing.

Nat Commun 2019 Apr 18;10(1):1817. Epub 2019 Apr 18.

Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, The Keith Peters Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK.

Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Huntington's disease manifest with the neuronal accumulation of toxic proteins. Since autophagy upregulation enhances the clearance of such proteins and ameliorates their toxicities in animal models, we and others have sought to re-position/re-profile existing compounds used in humans to identify those that may induce autophagy in the brain. A key challenge with this approach is to assess if any hits identified can induce neuronal autophagy at concentrations that would be seen in humans taking the drug for its conventional indication. Read More

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http://www.nature.com/articles/s41467-019-09494-2
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http://dx.doi.org/10.1038/s41467-019-09494-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472390PMC
April 2019
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Non-conventional compounds with potential therapeutic effects against Alzheimer's disease.

Expert Rev Neurother 2019 Apr 19. Epub 2019 Apr 19.

a Laboratory of Molecular Modeling, Department of Chemistry , Federal University of Lavras , Lavras/MG , 37200-000 , Brazil.

Introduction: Alzheimer's disease (AD) is the most common cause of dementia. Clinical progress in this pathogenesis field has drawn the attention of researchers, stimulating the investigation of novel treatment methods. Current therapies that deal with cholinesterase inhibitors and/or NMDA antagonists have shown a modest symptomatic potential, increasing the need for research into more efficient therapeutics. Read More

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http://dx.doi.org/10.1080/14737175.2019.1608823DOI Listing
April 2019
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Natural Products in Alzheimer's Disease Therapy: Would Old Therapeutic Approaches Fix the Broken Promise of Modern Medicines?

Molecules 2019 Apr 17;24(8). Epub 2019 Apr 17.

Pharmacognosy Research Laboratories & Herbal Analysis Services UK, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, UK.

Despite extensive progress in understanding the pathology of Alzheimer's disease (AD) over the last 50 years, clinical trials based on the amyloid-beta (Aβ) hypothesis have kept failing in late stage human trials. As a result, just four old drugs of limited clinical outcomes and numerous side effects are currently used for AD therapy. This article assesses the common pharmacological targets and therapeutic principles for current and future drugs. Read More

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http://dx.doi.org/10.3390/molecules24081519DOI Listing
April 2019
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Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral.

Molecules 2019 Apr 17;24(8). Epub 2019 Apr 17.

Department of Molecular and Translational Medicine, Division of Pharmacology, University of Brescia, 25123 Brescia, Italy.

Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO and SiO that generates cavities where water and other polar molecules or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). Read More

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https://www.mdpi.com/1420-3049/24/8/1517
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http://dx.doi.org/10.3390/molecules24081517DOI Listing
April 2019
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QuinoxalineTacrine QT78, a Cholinesterase Inhibitor as a Potential Ligand for Alzheimer's Disease Therapy.

Molecules 2019 Apr 17;24(8). Epub 2019 Apr 17.

Laboratory of Medicinal Chemistry (IQOG, CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain.

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer's disease therapy. We have found that is less toxic than tacrine at high concentrations (from 100 μM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC (hAChE) = 22.0 ± 1. Read More

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http://dx.doi.org/10.3390/molecules24081503DOI Listing

Systems Pharmacological Approach to Investigate the Mechanism of for Application to Alzheimer's Disease.

Molecules 2019 Apr 17;24(8). Epub 2019 Apr 17.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

(OC)-a traditional Chinese medicine (TCM)-has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer's disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood-brain barrier permeability against AD, by using a system network level-based in silico approach. Read More

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http://dx.doi.org/10.3390/molecules24081499DOI Listing
April 2019
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Refining memory assessment of elderly people with cognitive impairment: Insights from the short-term memory binding test.

Arch Gerontol Geriatr 2019 Apr 1;83:114-120. Epub 2019 Apr 1.

Department of Basic Psychology II (Cognitive Processes), Faculty of Psychology, Complutense University of Madrid, Spain.

Alzheimer's disease (AD) affects temporary memory for bound features more remarkably than for individual features. Such selective impairments manifest from presymptomatic through dementia stages via titration procedures. A recent study suggested that without titration and with high memory load the binding selectivity may disappear in people at risk of AD such as those with Mild Cognitive Impairment (MCI). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01674943193008
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http://dx.doi.org/10.1016/j.archger.2019.03.025DOI Listing
April 2019
2 Reads

Late-Life Environmental Enrichment Preserves Short-Term Memory and May Attenuate Microglia in Male APP/PS1 Mice.

Neuroscience 2019 Apr 15. Epub 2019 Apr 15.

Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Tasmania, 7000, Australia.

Environmental enrichment (EE) has been consistently reported to enhance cognitive function in mouse models of neuropathology. Microglia, implicated in Alzheimer's disease pathology, may mediate this effect. The aim of the present study was to investigate the effect of EE on cognitive function and microglia in mouse models of ageing and amyloidosis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03064522193025
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http://dx.doi.org/10.1016/j.neuroscience.2019.04.015DOI Listing
April 2019
2 Reads

Intravenous Infusion of Mesenchymal Stem Cells Improves Impaired Cognitive Function in a Cerebral Small Vessel Disease Model.

Neuroscience 2019 Apr 15. Epub 2019 Apr 15.

Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, 06516, USA.

Cerebral small vessel disease (CSVD) is not only a cause of vascular dementia (VD) but also a contributing factor to Alzheimer's disease (AD). The essential pathological feature of CSVD is the disruption of blood-brain barrier (BBB). Dysfunction of BBB due to degeneration of both endothelial cells and pericytes in capillaries leads to neuronal damage and progressive brain atrophy. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2019.04.018DOI Listing

Retinal oximetry: Metabolic imaging for diseases of the retina and brain.

Prog Retin Eye Res 2019 Apr 15. Epub 2019 Apr 15.

University of Iceland, Reykjavik, Iceland.

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of hemoglobin. The imaging technology is non-invasive and reproducible with remarkably low variability on test-retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic and brain disease. Read More

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http://dx.doi.org/10.1016/j.preteyeres.2019.04.001DOI Listing
April 2019
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Sex-Specific Neurogenic Deficits and Neurocognitive Disorders in Middle-Aged HIV-1 Tg26 Transgenic Mice.

Brain Behav Immun 2019 Apr 15. Epub 2019 Apr 15.

Center for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, United States; Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, United States. Electronic address:

Varying degrees of cognitive deficits affect over half of all HIV-1 infected patients. Because of antiretroviral treatment (ART) regimens, the HIV-1 patient population is increasing in age. Very few epidemiological studies have focused on sex-specific differences in HIV-1-associated neurocognitive disorders (HAND). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S08891591183060
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http://dx.doi.org/10.1016/j.bbi.2019.04.029DOI Listing
April 2019
2 Reads

Variability in the validity and reliability of outcome measures identified in a systematic review to assess treatment efficacy of cognitive enhancers for Alzheimer's Dementia.

PLoS One 2019 18;14(4):e0215225. Epub 2019 Apr 18.

Institute for Health Policy, Management & Evaluation, University of Toronto, Toronto, Ontario Canada.

Introduction: Selection of optimal outcome measures is a critical step in a systematic review; inclusion of uncommon or non-validated outcome measures can impact the uptake of systematic review findings. Our goals were to identify the validity and reliability of outcome measures used in primary studies to assess cognition, function, behaviour and global status; and, to use these data to select outcomes for a systematic review (SR) on treatment efficacy of cognitive enhancers for Alzheimer's Dementia (AD).

Methods: Articles fulfilling the eligibility criteria of the SR were included in a charting exercise to catalogue outcome measures reported. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215225PLOS
April 2019
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Behavioural and Psychological Symptoms in Neurocognitive Disorders: Specific Patterns in Dementia Subtypes.

Open Med (Wars) 2019 4;14:307-316. Epub 2019 Apr 4.

Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Egyetem tér 1, H-4032, Hungary.

Background: Behavioural and psychological symptoms in dementia (BPSD) form an important sub-syndrome of dementia. We assessed the frequency and severity of BPSD in a random sample of Hungarian treatment-naïve dementia patients. Furthermore, we examined the relationship between cognitive symptoms and BPSD and the pattern of BPSD in specific types of dementias. Read More

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http://www.degruyter.com/view/j/med.2019.14.issue-1/med-2019
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http://dx.doi.org/10.1515/med-2019-0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463819PMC
April 2019
1 Read

Novel Sustainable-by-Design HDAC Inhibitors for the Treatment of Alzheimer's Disease.

ACS Med Chem Lett 2019 Apr 29;10(4):671-676. Epub 2019 Mar 29.

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy.

Alzheimer's disease (AD) represents a global problem, with an estimation of the majority of dementia patients in low- and middle-income countries by 2050. Thus, the development of sustainable drugs has attracted much attention in recent years. In light of this, taking inspiration from the HDAC inhibitor vorinostat (), we develop the first HDAC inhibitors derived from cashew nut shell liquid (CNSL), an inexpensive agro-food waste material. Read More

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http://dx.doi.org/10.1021/acsmedchemlett.9b00071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466821PMC
April 2019
1 Read

Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis.

BMJ 2019 04 17;365:l1495. Epub 2019 Apr 17.

Biomedicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Objective: To examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia.

Design: Meta-analysis of 19 prospective observational cohort studies.

Data Sources: The Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies. Read More

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http://www.bmj.com/lookup/doi/10.1136/bmj.l1495
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http://dx.doi.org/10.1136/bmj.l1495DOI Listing
April 2019
3 Reads

Immune Signaling in Neurodegeneration.

Immunity 2019 Apr;50(4):955-974

Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. Electronic address:

Neurodegenerative diseases of the central nervous system progressively rob patients of their memory, motor function, and ability to perform daily tasks. Advances in genetics and animal models are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis; however, the role of cytokines, growth factors, and other immune signaling pathways in disease pathogenesis is still being examined. Here we review recent genetic risk and genome-wide association studies and emerging mechanisms for three key immune pathways implicated in disease, the growth factor TGF-β, the complement cascade, and the extracellular receptor TREM2. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.016DOI Listing

Strength training and running elicit different neuroprotective outcomes in a β-amyloid peptide-mediated Alzheimer's disease model.

Physiol Behav 2019 Apr 14. Epub 2019 Apr 14.

Applied Neuromechanics Group, Federal University of Pampa, Uruguaiana, 97501-970, Brazil. Electronic address:

Aerobic exercise induces neuroprotection, but few studies investigated whether strength training has similar potential. Here we examine whether effects of strength training differ from those of running training concerning cognitive symptomatology, oxidative stress and cholinergic status in a model of AD-like cognitive impairment induced by intrahippocampal infusion of a mix of β-amyloid peptides (Aβ) in rats. Male Wistar rats were submitted to 8 weeks of running exercise (RunEx; 40 min sessions at 70% of indirect VO max, 3 times/week) or strength exercise (StrEx; 3 sessions/week, 12 repetitions in 8 sets, 2 sets with repetitions at 50%, 2 at 75%, 2 at 90% and 2 at 100% of the maximum load), followed by Aβ infusion in the dorsal hippocampus. Read More

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http://dx.doi.org/10.1016/j.physbeh.2019.04.012DOI Listing
April 2019
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Predicting Early Mild Cognitive Impairment With Free Recall: The Primacy of Primacy.

Arch Clin Neuropsychol 2019 Apr 17. Epub 2019 Apr 17.

School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool, UK.

Objectives: Serial position effects have been found to discriminate between normal and pathological aging, and to predict conversion from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD). Different scoring methods have been used to estimate the accuracy of these predictions. In the current study, we investigated delayed primacy as predictor of progression to early MCI over established diagnostic memory methods. Read More

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https://academic.oup.com/acn/advance-article/doi/10.1093/arc
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http://dx.doi.org/10.1093/arclin/acz013DOI Listing
April 2019
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Lysosome-targeted carbon dots for ratiometric imaging of formaldehyde in living cells.

Nanoscale 2019 Apr 17. Epub 2019 Apr 17.

School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99164, USA.

Formaldehyde (FA) is involved in many biological processes and is closely connected with many diseases including Alzheimer's disease and cancer. Therefore, methods for sensitive and selective detection of FA in living cells are highly demanded. As a new class of carbon nanomaterials, carbon dots (CDs) have attracted great attention owing to their robust photostability, good biocompatibility and environmental friendliness. Read More

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http://xlink.rsc.org/?DOI=C9NR01678C
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http://dx.doi.org/10.1039/c9nr01678cDOI Listing
April 2019
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Dementia Friendly Communities in England: A scoping study.

Int J Geriatr Psychiatry 2019 Apr 16. Epub 2019 Apr 16.

University of Hertfordshire, Hatfield, UK.

Objectives: To describe the characteristics of Dementia Friendly Communities (DFCs) across England, in order to inform a national evaluation of their impact on the lives of those affected by dementia.

Methods: DFCs in England were identified through online searches and Alzheimer's Society records. A sub-sample (n=100) were purposively selected for in-depth study based on online searches and, where necessary, follow-up telephone calls. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/gps.5123
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http://dx.doi.org/10.1002/gps.5123DOI Listing
April 2019
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Using Turmeric Oil as a Solvent Improves the Distribution of Sesamin-Sesamolin in the Serum and Brain of Mice.

Lipids 2019 Apr 17. Epub 2019 Apr 17.

Department of Applied Biological Chemistry, Faculty of Agriculture, Kindai University, 204-3327 Nakamachi, Nara City, Nara, 631-8505, Japan.

Accumulation of amyloid-β peptide is associated with Alzheimer's dementia. Previously, we reported that sesamin and sesamolin inhibited β-secretase activity in vitro, and each was transported to the serum and brain in mice after oral administration. However, the bioavailability of sesamin and sesamolin was poor in mice. Read More

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http://dx.doi.org/10.1002/lipd.12147DOI Listing

Preparation and Characterization of Curcumin-Loaded Polymeric Nanomicelles to Interference with Amyloidogenesis through Glycation Method.

Biotechnol Appl Biochem 2019 Apr 16. Epub 2019 Apr 16.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), P.O. Box 14155-4777, Tehran, Iran.

Amyloid fibrils, including β-amyloid (Aβ) fibrils, are protein aggregates that form under certain conditions, associated with neurodegeneration that interfere with neural synaptic transmission resulting in some neural disorders, such as Alzheimer disease. The aim of this study is to inhibit amyloidogenesis by using preparatory polymeric nanomicelles as therapeutic agents and also as nano carriers for curcumin to target Aβ fibrils through the glycation method of Bovine Serum Albumin (BSA) in the presence of Phosphate Buffer Saline (PBS). Polymeric nanomicelles were prepared from Phosphatidylethanolamine-distearoyl methoxypolyethylene glycol conjugates in the presence and absence of Curcumin and then the morphological and structural characteristics of the nanomicelles were characterized in detail. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/bab.1751
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http://dx.doi.org/10.1002/bab.1751DOI Listing
April 2019
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Biological Hallmarks of Cancer in Alzheimer's Disease.

Mol Neurobiol 2019 Apr 16. Epub 2019 Apr 16.

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.

Although Alzheimer's disease (AD) is an international health research priority for our aging population, little therapeutic progress has been made. This lack of progress may be partially attributable to disease heterogeneity. Previous studies have identified an inverse association of cancer and AD, suggesting that cancer history may be one source of AD heterogeneity. Read More

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http://dx.doi.org/10.1007/s12035-019-1591-5DOI Listing
April 2019
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Long-term thiazide use and risk of low-energy fractures among persons with Alzheimer's disease-nested case-control study.

Osteoporos Int 2019 Apr 16. Epub 2019 Apr 16.

School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

We investigated the association between thiazide use and the risk of low-energy fractures among community dwellers with Alzheimer's disease. Longer use was associated with a decreased risk of low-energy fractures. This study extends the previous knowledge of reduced fracture risk of thiazides to persons with Alzheimer's disease. Read More

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http://dx.doi.org/10.1007/s00198-019-04957-0DOI Listing

eBrain: a Three Dimensional Simulation Tool to Study Drug Delivery in the Brain.

Authors:
Yaki Setty

Sci Rep 2019 Apr 16;9(1):6162. Epub 2019 Apr 16.

Gateway Institute for Brain Research, 3321 College Avenue, Davie, 33314, Florida, USA.

Neurodegenerative disorders such as Alzheimer's and Parkinson's disease are severe disorders with acute symptoms that gradually progress. In the course of developing disease-modifying treatments for neurodegenerative disorders there is a need to develop novel strategies to increase efficacy of drugs and accelerate the development process. We developed a tool for simulating drug delivery in the brain by translating MRI data into an interactive 3D model. Read More

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http://www.nature.com/articles/s41598-019-42261-3
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http://dx.doi.org/10.1038/s41598-019-42261-3DOI Listing
April 2019
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Publisher Correction: Pattern of Altered Plasma Elemental Phosphorus, Calcium, Zinc, and Iron in Alzheimer's Disease.

Sci Rep 2019 Apr 16;9(1):6343. Epub 2019 Apr 16.

King's College London, Department of Neuroimaging, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, London, SE5 8AF, UK.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. Read More

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http://dx.doi.org/10.1038/s41598-019-42217-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467863PMC

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory.

Nat Commun 2019 Apr 16;10(1):1766. Epub 2019 Apr 16.

Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377, Munich, Germany.

The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer's disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Read More

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http://www.nature.com/articles/s41467-019-09564-5
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http://dx.doi.org/10.1038/s41467-019-09564-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467911PMC
April 2019
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Ultrastructural evidence of microglial heterogeneity in Alzheimer's disease amyloid pathology.

J Neuroinflammation 2019 Apr 16;16(1):87. Epub 2019 Apr 16.

Axe neurosciences, Centre de recherche du CHU de Québec-Université Laval, 2705, boulevard Laurier, T2-50, Quebec, QC, G1V 4G2, Canada.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by the deposition of extracellular fibrillar amyloid β (fΑβ) and the intracellular accumulation of neurofibrillary tangles. As AD progresses, Aβ drives a robust and prolonged inflammatory response via its recognition by microglia, the brain's immune cells. Microglial reactivity to fAβ plaques may impair their normal surveillance duties, facilitating synaptic loss and neuronal death, as well as cognitive decline in AD. Read More

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http://dx.doi.org/10.1186/s12974-019-1473-9DOI Listing
April 2019
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How pattern information analyses of semantic brain activity elicited in language comprehension could contribute to the early identification of Alzheimer's Disease.

Neuroimage Clin 2019 Mar 26;22:101788. Epub 2019 Mar 26.

Department of Neuroscience, University of Rochester Medical Center, United States of America; School of Nursing, University of Rochester Medical Center, United States of America; Department of Psychiatry, University of Rochester Medical Center, United States of America; Department of Neurology, University of Rochester Medical Center, United States of America; Department of Brain and Cognitive Sciences, University of Rochester, United States of America. Electronic address:

Alzheimer's disease (AD) is associated with a loss of semantic knowledge reflecting brain pathophysiology that begins years before dementia. Identifying early signs of pathophysiology induced dysfunction in the neural systems that access and process words' meaning could therefore help forecast dementia. This article reviews pioneering studies demonstrating that abnormal functional Magnetic Resonance Imaging (fMRI) response patterns elicited in semantic tasks reflect both AD-pathophysiology and the hereditary risk of AD, and also can help forecast cognitive decline. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451171PMC

Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer's disease.

Neuroimage Clin 2019 Apr 3;22:101812. Epub 2019 Apr 3.

Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.

We studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) compared to controls, how it differs between the two dementia subtypes, and a possible relation between dynamic connectivity alterations and temporally transient clinical symptoms in DLB. Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analyzed using dual regression to determine between-network functional connectivity. Subsequently, we used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101812DOI Listing
April 2019
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Attention network dysfunction underlies memory impairment in posterior cortical atrophy.

Neuroimage Clin 2019 Mar 13;22:101773. Epub 2019 Mar 13.

Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK; Research Institute for the Care of the Elderly, Royal United Hospital, Bath, UK. Electronic address:

Accumulating evidence suggests that memory is impaired in posterior cortical atrophy (PCA), alongside the early and defining visual disorder. The posterior parietal cortex is a key region of pathology in PCA and memory impairment may be the result of dysfunction of parietally dependent network function rather than the medial temporal lobe dependent dysfunction that defines the storage deficits in typical Alzheimer's disease. We assessed episodic memory performance and network function in16 PCA patients and 19 healthy controls who underwent structural and resting-state functional MRI and neuropsychological testing. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22131582193012
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http://dx.doi.org/10.1016/j.nicl.2019.101773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453667PMC
March 2019
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APOE-ε4 risk variant for Alzheimer's disease modifies the association between cognitive performance and cerebral morphology in healthy middle-aged individuals.

Neuroimage Clin 2019 Apr 8;23:101818. Epub 2019 Apr 8.

Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain; Universitat Pompeu Fabra, Barcelona, Spain. Electronic address:

The APOE-ε4 genotype is the highest genetic risk factor for Alzheimer's disease (AD). In cognitively unimpaired individuals, it has been related to altered brain morphology, function and earlier amyloid beta accumulation. However, its impact on cognitive performance is less evident. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101818DOI Listing
April 2019
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Peri-Infarct Upregulation of the Oxytocin Receptor in Vascular Dementia.

J Neuropathol Exp Neurol 2019 May;78(5):436-452

Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, Michigan.

Vascular dementia (VaD) is cognitive decline linked to reduced cerebral blood perfusion, yet there are few therapeutic options to protect cognitive function following cerebrovascular accidents. The purpose of this study was to profile gene expression changes unique to VaD to identify and characterize disease relevant changes that could offer clues for future therapeutic direction. Microarray-based profiling and validation studies of postmortem frontal cortex samples from VaD, Alzheimer disease, and age-matched control subjects revealed that the oxytocin receptor (OXTR) was strongly and differentially upregulated in VaD. Read More

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http://dx.doi.org/10.1093/jnen/nlz023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467199PMC
May 2019
1 Read