102,086 results match your criteria Alzheimer Disease in Individuals With Down Syndrome


Impairment in complex activities of daily living is related to neurodegeneration in Alzheimer's disease-specific regions.

Neurobiol Aging 2018 Nov 26;75:109-116. Epub 2018 Nov 26.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology & Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Impairment in instrumental activities of daily living (IADL) is an early clinical feature of Alzheimer's disease (AD). The neurobiology underlying IADL disruptions is still unclear. We aimed to investigate the relationship between IADL functioning and cortical atrophy across the AD spectrum. Read More

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November 2018

A multiomic approach to characterize the temporal sequence in Alzheimer's disease-related pathology.

Neurobiol Dis 2018 Dec 14. Epub 2018 Dec 14.

Institute of Biomedicine, University of Eastern Finland, Kuopio 70210, Finland. Electronic address:

No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer's disease (AD). Here, we coupled transcriptomic and phosphoproteomic approaches to determine the temporal sequence of changes in mRNA, protein, and phosphopeptide expression levels from human temporal cortical samples, with varying degree of AD-related pathology. This approach highlighted fluctuation in synaptic and mitochondrial function as the earliest pathological events in brain samples with AD-related pathology. Read More

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December 2018

Cerebrospinal fluid ferritin levels predict brain hypometabolism in people with underlying β-amyloid pathology.

Neurobiol Dis 2018 Dec 14. Epub 2018 Dec 14.

Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia; Cooperative Research Center for Mental Health, Victoria, Australia. Electronic address:

β-Amyloid pathology is elevated in ~30% of cognitively normal people over 65, and is associated with accelerated neurodegeneration in the pre-clinical stages of Alzheimer's disease. Recent findings reveal that brain iron might also act to propel neurodegeneration in people with underlying amyloid pathology. Here, repeated PET scans of fluorodeoxyglucose (FDG) were used as a biomarker for brain hypometabolism and a downstream biomarker of neurodegeneration to investigate whether levels of ferritin in the cerebrospinal fluid (CSF; a reporter of brain iron load) are associated with prodromal disease progression of people with high β-amyloid pathology determined by established cut-off values in CSF t-tau/Aβ ratio. Read More

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December 2018

Understanding and predicting the longitudinal course of dementia.

Curr Opin Psychiatry 2018 Dec 14. Epub 2018 Dec 14.

Centre for Dementia Prevention, University of Edinburgh, Edinburgh, UK.

Purpose Of Review: To date, most research in dementia has focused either on the identification of dementia risk prediction or on understanding changes and predictors experienced by individuals before diagnosis. Despite little is known about how individuals change after dementia diagnosis, there is agreement that changes occur over different time scales and are multidomain. In this study, we present an overview of the literature regarding the longitudinal course of dementia. Read More

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December 2018

Chemicals, somatic mutations and neurodegeneration: Evidence from Western Pacific ALS-PDC.

Neuropathol Appl Neurobiol 2018 Dec 17. Epub 2018 Dec 17.

Department of Neurology, School of Medicine and Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon, USA.

Leija-Salazar and colleagues discuss current evidence for somatic mutations in neurodegeneration, focusing on sporadic, usually late-onset neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson disease (PD) and Alzheimer's disease (AD). Somatic mutation, defined as any acquired post-zygotic change in the nuclear genome, has long been linked to chemically induced DNA damage, aging and cancer but little more than a theoretical basis exists to associate comparable phenomena with sporadic neurodegenerative diseases. Whereas specific exogenous mutagenic chemicals, such as the fungal toxin aflatoxin B1, the amine dye benzo(a)-pyrene, and a tobacco-specific N-nitrosamine, are key examples of proven mutagenic carcinogens [2], only broad exposure categories, such as tobacco smoke, have been linked positively with ALS and AD, and negatively with PD. Read More

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December 2018

miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3β in Alzheimer's disease.

J Cell Biochem 2018 Dec 16. Epub 2018 Dec 16.

Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

As the most common neurodegenerative disease, Alzheimer's disease (AD) is characterized by memory, perception, and behavioral damage, which may ultimately lead to emotional fluctuation and even lethal delirium. Increasing studies indicate that microRNAs (miRNAs) are associated with pathological features of AD. However, the role of miR-219-5p in AD progression is still unclear. Read More

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December 2018

CSF total tau levels are associated with hippocampal novelty irrespective of hippocampal volume.

Alzheimers Dement (Amst) 2018 2;10:782-790. Epub 2018 Nov 2.

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Introduction: We examined the association between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, neural novelty responses, and brain volume in predementia old age.

Methods: We conducted a cross-sectional analysis of the observational, multicentric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Seventy-six participants completed task functional magnetic resonance imaging and provided CSF (40 cognitively unimpaired, 21 experiencing subjective cognitive decline, and 15 with mild cognitive impairment). Read More

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November 2018

Changes in Serine Racemase-Dependent Modulation of NMDA Receptor: Impact on Physiological and Pathological Brain Aging.

Front Mol Biosci 2018 28;5:106. Epub 2018 Nov 28.

UNICAEN, INSERM, COMETE, Normandie University, Caen, France.

The N-methyl-D-Aspartate glutamate receptors (NMDARs) are pivotal for the functional and morphological plasticity that are required in neuronal networks for efficient brain activities and notably for cognitive-related abilities. Because NMDARs are heterogeneous in subunit composition and associated with multiple functional regulatory sites, their efficacy is under the tonic influence of numerous allosteric modulations, whose dysfunction generally represents the first step generating pathological states. Among the enzymatic candidates, serine racemase (SR) has recently gathered an increasing interest considering that it tightly regulates the production of d-serine, an amino acid now viewed as the main endogenous co-agonist necessary for NMDAR activation. Read More

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November 2018

Effects of rising amyloidβ levels on hippocampal synaptic transmission, microglial response and cognition in APP/PSEN1 transgenic mice.

EBioMedicine 2018 Dec 13. Epub 2018 Dec 13.

Department of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address:

Background: Progression of Alzheimer's disease is thought initially to depend on rising amyloidβ and its synaptic interactions. Transgenic mice (TASTPM; APP/PSEN1) show altered synaptic transmission, compatible with increased physiological function of amyloidβ, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Read More

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December 2018

Subjective cognitive decline and rates of incident Alzheimer's disease and non-Alzheimer's disease dementia.

Alzheimers Dement 2018 Dec 13. Epub 2018 Dec 13.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. Electronic address:

Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia.

Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Read More

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December 2018

Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Alzheimers Dement 2018 Dec 13. Epub 2018 Dec 13.

Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA. Electronic address:

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz. Read More

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December 2018

Subregional volume reduction of the cholinergic forebrain in subjective cognitive decline (SCD).

Neuroimage Clin 2018 Nov 27:101612. Epub 2018 Nov 27.

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department of Psychiatry, Medical Faculty, University of Cologne, Germany.

Subjective cognitive decline (SCD) patients are considered as a risk population for preclinical Alzheimer's Disease (AD). Supporting this idea, previous studies in SCD populations report subtle alterations in various cognitive and neuroimaging biomarkers that are typically affected during AD progression. To extend these observations, the present study examined whether SCD patients show atrophy of cholinergic basal forebrain nuclei (chBFN), analogous with recent findings in prodromal and clinical AD patients. Read More

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November 2018

Intranasal insulin activates Akt2 signaling pathway in the hippocampus of wild-type but not in APP/PS1 Alzheimer model mice.

Neurobiol Aging 2018 Nov 17;75:98-108. Epub 2018 Nov 17.

Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address:

Type 2 diabetes mellitus (T2DM) increases the risk for Alzheimer's disease (AD). Human AD brains show reduced glucose metabolism as measured by [18F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET). Here, we used 14-month-old wild-type (WT) and APP/PS1 (APP/PS1) transgenic mice to investigate how a single dose of intranasal insulin modulates brain glucose metabolism using FDG-PET and affects spatial learning and memory. Read More

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November 2018
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The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease.

Nutrition 2018 Oct 10;60:118-121. Epub 2018 Oct 10.

Department of Psychology, University of Canterbury, Christchurch, New Zealand.

The prevalence of Alzheimer's disease, a chronic neurodegenerative condition, is increasing as is the need for effective treatments and preventions. The underlying pathology of Alzheimer's is not yet fully understood, so existing research has focused on understanding the prominent features of the disease. These include amyloid plaques, which accumulate in the brains of those with Alzheimer's disease; impaired glucose metabolism; and neuronal cell death. Read More

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October 2018
2 Reads

Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors.

Gene 2018 Dec 13. Epub 2018 Dec 13.

Department of Pharmacology, Faculty of Pharmacy, Marmara University, Istanbul, Turkey.

Alzheimer's disease is a progressive neurodegenerative disorder causing common health problem with increasing age. Evidences show that the key symptoms of AD are mainly caused by cholinergic system dysfunction which has a role in cognitive disorders. Cholinergic pathways especially muscarinic receptors like M subtype also have a major role in learning, memory, cognitive functions and emotional state. Read More

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December 2018

Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI.

Neuroimage 2018 Dec 13. Epub 2018 Dec 13.

F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (-3. Read More

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December 2018

Novel antibody against oligomeric amyloid-β: Insight into factors for effectively reducing the aggregation and cytotoxicity of amyloid-β aggregates.

Int Immunopharmacol 2018 Dec 13;67:176-185. Epub 2018 Dec 13.

Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, China; School of Life Science, Jilin University, Changchun, China. Electronic address:

Amyloid-beta 42 (Aβ42) aggregates represent a prominent histopathological feature in Alzheimer's disease (AD); thus, immunotherapy against oligomeric Aβ42 aggregates is considered to be a potentially safe and specific therapeutic strategy. In this study, we identified an anti-oligomeric Aβ42 aggregate single-chain variable fragment (scFv) antibody, HT6, that is capable of efficiently binding to medium-sized Aβ42 aggregates (mainly 18-45 kDa) in vitro with an equilibrium dissociation constant (K) of 3.0 × 10 M, whether they were derived from Aβ42 monomer, larger Aβ42 oligomers, or even fibrils. Read More

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December 2018

Differential accumulation of Tau phosphorylated at residues Thr231, Ser262 and Thr205 in hippocampal interneurons and its modulation by Tau mutations (VLW) and amyloid-β peptide.

Neurobiol Dis 2018 Dec 13. Epub 2018 Dec 13.

Department of Cell Biology, Physiology and Immunology, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain; Vall d'Hebron Institute of Research, Barcelona, Spain. Electronic address:

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated Tau protein (P-Tau). Our recent data showed a differential accumulation of Tau protein phosphorylated at Thr231 in distinct hippocampal neurons in VLW mice-an animal model that overexpresses mutated human Tau. Here we demonstrate that, in VLW mice, the accumulation of human P-Tau in the pyramidal cells induces the phosphorylation of murine Tau at Thr231 (pThr231) in hippocampal interneurons. Read More

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December 2018

Prognosis of conversion of mild cognitive impairment to Alzheimer's dementia by voxel-wise Cox regression based on FDG PET data.

Neuroimage Clin 2018 Dec 10:101637. Epub 2018 Dec 10.

Department of Nuclear Medicine, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany; Center for Geriatrics and Gerontology Freiburg, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany.

Aim: The value of F-fluorodeoxyglucose (FDG) PET for the prognosis of conversion from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. In the present work, the identification of cerebral metabolic patterns with significant prognostic value for conversion of MCI patients to AD is investigated with voxel-based Cox regression, which in contrast to common categorical comparisons also utilizes time information.

Methods: FDG PET data of 544 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were randomly split into two equally-sized datasets (training and test). Read More

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December 2018

Automated and manual hippocampal segmentation techniques: Comparison of results, reproducibility and clinical applicability.

Neuroimage Clin 2018 Oct 14:101574. Epub 2018 Oct 14.

Department of Neurology, Indiana University, Indianapolis, IN, USA; Department of Radiological Sciences, Indiana University, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA. Electronic address:

Background: Imaging techniques used to measure hippocampal atrophy are key to understanding the clinical progression of Alzheimer's disease (AD). Various semi-automated hippocampal segmentation techniques are available and require human expert input to learn how to accurately segment new data. Our goal was to compare 1) the performance of our automated hippocampal segmentation technique relative to manual segmentations, and 2) the performance of our automated technique when provided with a training set from two different raters. Read More

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October 2018

Influence of hypertension on brain amyloid deposition and Alzheimer's disease signature neurodegeneration.

Neurobiol Aging 2018 Nov 16;75:62-70. Epub 2018 Nov 16.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

This study aimed to investigate the relationship of hypertension with beta-amyloid (Aβ) and neurodegeneration biomarkers of Alzheimer's disease (AD) and the modulating effect of apolipoprotein E-ε4 (APOE4). In total, 259 cognitively normal (CN) and 79 AD dementia older adults received clinical assessments including the evaluation for the presence of hypertension, [C]-Pittsburgh-compound-B-positron emission tomography, magnetic resonance imaging, and APOE genotyping. We used a clinical stage-specific approach, separately focusing on CN and AD dementia stages. Read More

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November 2018

Synthesis and evaluation of clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands for the treatment of Alzheimer's disease.

Eur J Med Chem 2018 Dec 7;163:512-526. Epub 2018 Dec 7.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address:

Considering the importance of PDE4D inhibition and the modulation of biometals in Alzheimer's disease (AD) therapeutics, we have designed, synthesized and evaluated a series of new clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands for the treatment of AD. In vitro studies demonstrated that some of the molecules processed remarkable inhibitory activity against phosphodiesterase 4D (PDE4D), strong intracellular antioxidant capacity, potent inhibition of metal-induced aggregation of Aβ, and potential blood-brain barrier permeability. Compound 7a demonstrated significant improvement in cognitive and spatial memory in an Aβ-induce mouse model in Morris water-maze test (MWM). Read More

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December 2018

CSF-ApoER2 fragments as a read-out of reelin signaling: Distinct patterns in sporadic and autosomal-dominant Alzheimer disease.

Clin Chim Acta 2018 Dec 12. Epub 2018 Dec 12.

Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 Sant Joan d'Alacant, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address:

Reelin is a glycoprotein associated with synaptic plasticity and neurotransmission. The malfunctioning of reelin signaling in the brain is likely to contribute to the pathogenesis of Alzheimer's disease (AD). Reelin binding to Apolipoprotein E receptor 2 (ApoER2) activates downstream signaling and induces the proteolytic cleavage of ApoER2, resulting in the generation of soluble fragments. Read More

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December 2018
5 Reads

Neuroprotective effects of 1`δ-1`-acetoxyeugenol acetate on Aβ induced cognitive dysfunction in mice.

Biomed Pharmacother 2019 Jan 13;109:1454-1461. Epub 2018 Nov 13.

Department of Pharmacology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India. Electronic address:

The progressive accumulation of amyloid beta (Aβ) peptide is neurotoxic and leads to Alzheimer's type dementia. Accumulation of Aβ has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1`δ-1`-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L. Read More

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January 2019

Protective and reversal actions of a novel peptidomimetic against a pivotal toxin implicated in Alzheimer's disease.

Biomed Pharmacother 2019 Jan 6;109:1052-1061. Epub 2018 Nov 6.

Neuro-Bio Ltd, Culham Science Centre, Building F5, Abingdon, OX14 3DB, UK.

Despite the many attempts to understand the aetiology of Alzheimer's disease, the basic mechanisms accounting for the progressive cycle of neuronal loss are still unknown. Previous work has suggested that the pivotal molecule mediating neurodegeneration could be an independently acting peptide cleaved from acetylcholinesterase. This previously unidentified agent acts as a signalling molecule in selectively vulnerable groups of cells where erstwhile developmental mechanisms are activated inappropriately to have a toxic effect in the context of the mature brain. Read More

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January 2019

Striking reduction in neurons and glial cells in anterior thalamic nuclei of older patients with Down syndrome.

Neurobiol Aging 2018 Nov 17;75:54-61. Epub 2018 Nov 17.

School of Psychology, Cardiff University, Cardiff, UK. Electronic address:

The anterior thalamic nuclei are important for spatial and episodic memory, however, surprisingly little is known about the status of these nuclei in neurological conditions that present with memory impairments, such as Down syndrome. We quantified neurons and glial cells in the anterior thalamic nuclei of four older patients with Down syndrome. There was a striking reduction in the volume of the anterior thalamic nuclei and this appeared to reflect the loss of approximately 70% of neurons. Read More

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November 2018

Phenotypic variability and neuropsychological findings associated with C9orf72 repeat expansions in a Bulgarian dementia cohort.

PLoS One 2018 14;13(12):e0208383. Epub 2018 Dec 14.

Karolinska Institutet, Dept NVS, Division for Neurogeriatrics, Bioclinicum, Akademiska stråket, Solna, Sweden.

Background: The GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in several European populations. The objective of this study was to determine the frequency of C9orf72 repeat expansions in a Bulgarian dementia cohort and to delineate the associated clinical features.

Methods And Findings: PCR-based assessments of the C9orf72 hexanucleotide repeat expansion in all study samples (including 82 FTD, 37 Alzheimer's disease (AD), and 16 other neurodegenerative/dementia disorder cases) were performed. Read More

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December 2018

Gene mutations in a Han Chinese Alzheimer's disease cohort.

Brain Behav 2018 Dec 14:e01180. Epub 2018 Dec 14.

Department of Neurology, Xinxiang Medical University, Xinxiang, China.

Objective: Alzheimer's disease (AD) is the most common form of dementia characterized by memory loss at disease onset. The gene mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the frequent causes of AD. However, the clinical and genetic features of AD overlap with other neurodegenerative diseases. Read More

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December 2018

The impact of Aβ and tau on prospective cognitive decline in older individuals.

Ann Neurol 2018 Dec 14. Epub 2018 Dec 14.

Harvard Aging Brain Study, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objectives: Amyloid-beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at post-mortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated.

Methods: One hundred and thirty-seven older individuals (age=76. Read More

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December 2018

Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease.

Hum Brain Mapp 2018 Dec 13. Epub 2018 Dec 13.

Department of Radiology, Mayo Clinic, Rochester, Minnesota.

Alzheimer's disease (AD) can present with atypical clinical forms where the prominent domain of deficit is not memory, that is, atypical AD. Atypical AD patients show cortical atrophy on MRI, hypometabolism on [ F]fluorodeoxyglucose (FDG) PET, tau uptake on [ F]AV-1451 PET, and white matter tract degeneration on diffusion tensor imaging (DTI). How these disease processes relate to each other locally and distantly remains unclear. Read More

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December 2018

Tadalafil: 15 years' journey in male erectile dysfunction and beyond.

Authors:
Nermin S Ahmed

Drug Dev Res 2018 Dec 13. Epub 2018 Dec 13.

Faculty of Pharmacy and Biotechnology, Department of Pharmaceutical Chemistry, German University in Cairo, Cairo, Egypt.

Hit, Lead & Candidate Discovery Tadalafil, Cialis, Eli Lilly & Co./ICOS, (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6] pyrido[3,4-b]indole-1,4-dione, was first discovered in 2003. It was reported to have high diastereospecificity for phosphodiesterase 5 (PDE5) inhibitions. Read More

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December 2018
3 Reads

Optical coherence tomography in the investigation of systemic neurologic disease.

Clin Exp Optom 2018 Dec 11. Epub 2018 Dec 11.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.

Optical coherence tomography (OCT) is a well-established technique for the clinical examination, diagnosis, severity staging and monitoring of ophthalmic disorders. The application of this technology has more recently been extended beyond ophthalmic disease, whereby it has been demonstrated that OCT can serve as an ophthalmic marker for a range of systemic neurodegenerative disorders, such as Parkinson's disease, multiple sclerosis, Alzheimer's disease and diabetic peripheral neuropathy. This review will focus on the clinical utility of OCT-derived retinal measures for the investigation of these conditions. Read More

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December 2018

The emerging role of microRNA-4487/6845-3p in Alzheimer's disease pathologies is induced by Aβ25-35 triggered in SH-SY5Y cell.

BMC Syst Biol 2018 Dec 14;12(Suppl 7):119. Epub 2018 Dec 14.

Department of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China.

Background: Accumulation of amyloid β-peptide (Aβ) is implicated in the pathogenesis and development of Alzheimer's disease (AD). Neuron-enriched miRNA was aberrantly regulated and may be associated with the pathogenesis of AD. However, regarding whether miRNA is involved in the accumulation of Aβ in AD, the underlying molecule mechanism remains unclear. Read More

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December 2018
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Novel tau fragments in cerebrospinal fluid: relation to tangle pathology and cognitive decline in Alzheimer's disease.

Acta Neuropathol 2018 Dec 13. Epub 2018 Dec 13.

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Göteborgsvägen 31, House V3/SU, 43180, Mölndal, Sweden.

Tau is an axonal microtubule-binding protein. Tau pathology in brain and increased tau concentration in the cerebrospinal fluid (CSF) are hallmarks of Alzheimer's disease (AD). Most of tau in CSF is present as fragments. Read More

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December 2018
2 Reads

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study.

Dement Neuropsychol 2018 Oct-Dec;12(4):388-393

Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.

Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS.

Objective: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. Read More

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December 2018

Monitoring of drug treatment and psychosocial intervention with SPECT in Alzheimer patients Implications for neurologically appropriate psychosocial interventions. An observational study. The Osaki-Tajiri Project.

Dement Neuropsychol 2018 Oct-Dec;12(4):380-387

Geriatric Behavioral Neurology, Tohoku University CYRIC, Japan.

We previously examined cerebral blood flow (CBF) with single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD) with reference to drug treatment (donepezil) and psychosocial intervention.

Objective: The aim is to provide "brain-based" evidence for psychosocial interventions using SPECT.

Methods: The participants were 27 consecutive outpatients with AD who received the drug and psychosocial intervention, and SPECT three times (baseline, pre-/post-intervention) at 6 month-intervals. Read More

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December 2018

Focused ultrasound and Alzheimer's disease A systematic review.

Dement Neuropsychol 2018 Oct-Dec;12(4):353-359

Medical student. Departamento de Medicina, Faculdade de Ciências Médicas da Paraíba, Cabedelo, PB, Brazil.

Alzheimer's disease (AD) affects millions of people, however, there is still no effective treatment. The use of focused ultrasound with microbubbles (FUS-MB) for the opening of the blood-brain barrier has been recently studied and may become a promising therapeutic target.

Objective: To discuss the use of FUS-MB for the treatment of AD and to present some of the techniques used. Read More

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December 2018

Metamemory monitoring in Alzheimer's disease A systematic review.

Dement Neuropsychol 2018 Oct-Dec;12(4):337-352

PhD, Center for Alzheimer's disease and Related Disorders, Institute of Psychiatry, Universidade Federal do Rio de Janeiro, RJ, Brazil.

Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory system.

Objective: Metamemory is one's own knowledge and control of memory. A systematic review was performed to identify the types of tasks used for evaluating metamemory monitoring, the stimuli used in these tasks, their limitations and the outcomes in people with Alzheimer's disease (PwAD). Read More

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December 2018
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Neuroinflammation in mouse models of Alzheimer's disease.

Clin Exp Neuroimmunol 2018 Nov 23;9(4):211-218. Epub 2018 Sep 23.

RIKEN Center for Brain Science Laboratory for Proteolytic Neuroscience Wako Japan.

Alzheimer's disease (AD) is the most common type of neurocognitive disorder. Although both amyloid β peptide deposition and neurofibrillary tangle formation in the AD brain have been established as pathological hallmarks of the disease, many other factors contribute in a complex manner to the pathogenesis of AD before clinical symptoms of the disease become apparent. Longitudinal pathophysiological processes cause patients' brains to exist in a state of chronic neuroinflammation, with glial cells acting as key regulators of the neuroinflammatory state. Read More

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November 2018

Integrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP.

Transl Psychiatry 2018 Dec 13;8(1):265. Epub 2018 Dec 13.

Department of Psychiatry, Washington University School of Medicine, 660S. Euclid Ave. Campus Box 8134, St. Louis, MO, 63110, USA.

Mutations in the microtubule-associated protein tau (MAPT) gene cause autosomal dominant frontotemporal lobar degeneration with tau inclusions (FTLD-tau). MAPT p.R406W carriers present clinically with progressive memory loss and neuropathologically with neuronal and glial tauopathy. Read More

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December 2018
1 Read

Brain β-Amyloid and Atrophy in Individuals at Increased Risk of Cognitive Decline.

AJNR Am J Neuroradiol 2018 Dec 13. Epub 2018 Dec 13.

Division of Clinical Neurosciences (N.K., J.O.R.), Turku University Hospital, Turku, Finland.

Background And Purpose: The relationship between brain β-amyloid and regional atrophy is still incompletely understood in elderly individuals at risk of dementia. Here, we studied the associations between brain β-amyloid load and regional GM and WM volumes in older adults who were clinically evaluated as being at increased risk of cognitive decline based on cardiovascular risk factors.

Materials And Methods: Forty subjects (63-81 years of age) were recruited as part of a larger study, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability. Read More

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December 2018
1 Read

Diffusion MRI detects longitudinal white matter changes in the 3xTg-AD mouse model of Alzheimer's disease.

Magn Reson Imaging 2018 Dec 11;57:235-242. Epub 2018 Dec 11.

Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC, USA; Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.

The sensitivity of multiple diffusion MRI (dMRI) parameters to longitudinal changes in white matter microstructure was investigated for the 3xTg-AD transgenic mouse model of Alzheimer's disease, which manifests both amyloid beta plaques and neurofibrillary tangles. By employing a specific dMRI method known as diffusional kurtosis imaging, eight different diffusion parameters were quantified to characterize distinct aspects of water diffusion. Four female 3xTg-AD mice were imaged at five time points, ranging from 4. Read More

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December 2018

Air pollution and brain health: defining the research agenda.

Curr Opin Psychiatry 2018 Dec 14. Epub 2018 Dec 14.

Centre for Occupational and Environmental Health, University of Manchester, Manchester, UK.

Purpose Of Review: The literature on air pollution and brain health is rapidly expanding and it is a universal finding that greater exposure to air pollution is associated with worse outcomes, whatever the measure of brain health used (clinical dementia, neuroimaging correlates, or cognitive impairment). However, there are a number of important questions which the studies currently published are not able to answer: when in the life course does exposure to air pollution most have the most impact?; which pollutant(s) or components are most important?; and since dementia describes a heterogeneous group of conditions, which is most affected by exposure to air pollution?

Recent Findings: We briefly review and discuss the nine articles which have been published so far in 2018, so recently that they were not included in the four review articles also published this year. We highlight the variation in estimates of air pollution used but the consistency in deriving them from residential address (with or without some knowledge of an individual's previous home locations). Read More

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December 2018

Organotypic brain slices of ADULT transgenic mice: a tool to study Alzheimer´s disease.

Authors:
Christian Humpel

Curr Alzheimer Res 2018 Dec 12. Epub 2018 Dec 12.

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

Transgenic mice have been extensively used to study the Alzheimer pathology. In order to reduce, refine and replace (3Rs) the number of animals, ex vivo cultures are used and optimized. Organotypic brain slices are the most potent ex vivo slice culture models, keeping the 3-dimensional structure of the brain and being closest to the in vivo situation. Read More

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December 2018

The temporal relationship between pain intensity and pain interference and incident dementia.

Curr Alzheimer Res 2018 Dec 12. Epub 2018 Dec 12.

Saul B. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461 . United States.

Background: Chronic pain is common among older adults and is associated with cognitive dysfunction based on cross-sectional studies. However, the longitudinal association between chronic pain and incident dementia in community-based samples is unknown.

Objective: We aimed to evaluate the associations of pain intensity and pain interference with incident dementia in a community-based sample of older adults. Read More

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December 2018
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Outcomes of perilla seed oil as an additional neuroprotective therapy in patients with mild to moderate dementia: a randomized control trial.

Curr Alzheimer Res 2018 Dec 12. Epub 2018 Dec 12.

Thammasat University - Chulabhron International College of Medicine, Klonglaung, Pathum Thani. Thailand.

Background: Dementia is a common medical disorder in elderly. Oxidative stress plays a major role in the process of cognitive decline in dementia. Perilla seed oil demonstrates its neuroprotective effects via anti-oxidative mechanisms against dementia. Read More

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December 2018

Down-Regulation Of Mir-107 Worsen Spatial Memory By Suppressing SYK Expression And Inactivating NF-ΚB Signaling Pathway.

Curr Alzheimer Res 2018 Dec 12. Epub 2018 Dec 12.

Qingdao Mental Health Center, Qingdao 266000, Shandong. China.

Background:Alzheimer disease (AD) is a chronic progressive neurodegenerative disorder in central nervous system seen.

Objective: We aimed to study the miR-107 in Alzheimer's Disease (AD) pathology through regulating SYK and NF-κB signaling pathway.

Method: Bioinformatics analysis was performed to screen NF-κB signaling pathway and differentially expressed genes. Read More

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December 2018

Computational and in-vitro validation of natural molecules as potential Acetylcholinesterase inhibitors and neuroprotective agents.

Curr Alzheimer Res 2018 Dec 12. Epub 2018 Dec 12.

Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh - 173234. India.

Background: Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer's disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is to identify new and safer 'disease-modifying drugs'.

Methods: Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism. Read More

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December 2018

Accurate and Unbiased Quantitation of Amyloid-β Fluorescence Images Using ImageSURF.

Curr Alzheimer Res 2018 Dec 12. Epub 2018 Dec 12.

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

Background: Images of amyloid-β pathology characteristic of Alzheimer's disease are difficult to consistently and accurately segment, due to diffuse deposit boundaries and imaging variations.

Methods: We evaluated the performance of ImageSURF, our open-source ImageJ plugin, which considers a range of image derivatives to train image classifiers. We compared ImageSURF to standard image thresholding to assess its reproducibility, accuracy and generalizability when used on fluorescence images of amyloid pathology. Read More

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December 2018