99,311 results match your criteria Alzheimer's research & therapy[Journal]


Cardiovascular disease risk factor burden and cognition: Implications of ethnic diversity within the Hispanic Community Health Study/Study of Latinos.

PLoS One 2019 22;14(4):e0215378. Epub 2019 Apr 22.

Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois, United States of America.

Objective: Hispanics/Latinos have some of the highest prevalence rates for cardiovascular disease risk factors, but stark differences exist by self-reported background. Cardiovascular disease risk factors negatively impact cognition in Hispanics/Latinos; less is known about these relationships by Hispanic/Latino backgrounds. We investigated cognitive associations with cardiovascular disease risk factor burden in a diverse cohort, the Hispanic Community Health Study/Study of Latinos. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215378PLOS
April 2019
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A novel synbiotic delays Alzheimer's disease onset via combinatorial gut-brain-axis signaling in Drosophila melanogaster.

PLoS One 2019 22;14(4):e0214985. Epub 2019 Apr 22.

Biomedical and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and organs Research Center, Faculty of Medicine, McGill University, Montreal, Canada.

The gut-brain-axis (GBA) describing the bidirectional communication between the gut microbiota and brain was recently implicated in Alzheimer's disease (AD). The current study describes a novel synbiotic containing three metabolically active probiotics and a novel polyphenol-rich prebiotic which has beneficial impacts on the onset and progression of AD. In a transgenic humanized Drosophila melanogaster model of AD, the synbiotic increased survivability and motility and rescued amyloid beta deposition and acetylcholinesterase activity. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214985PLOS

Secondary Bleeding During Acute Experimental Intracerebral Hemorrhage.

Stroke 2019 May;50(5):1210-1215

From the Neurovascular Research Laboratory, Department of Radiology (F.S., M.B., T.Q., I.T., P.F., C.A.), Massachusetts General Hospital, Harvard Medical School, Charlestown.

Background and Purpose- Mechanisms contributing to acute hematoma growth in intracerebral hemorrhage are not well understood. Neuropathological studies suggest that the initial hematoma may create mass effect that can tear vessels in the vicinity by shearing, causing further bleeding and hematoma growth. Methods- To test this in mice, we simulated initial intracerebral hemorrhage by intrastriatal injection of a liquid polymer that coagulates upon contact with tissue and measured the presence and volume of bleeding secondary to the mass effect using Hemoglobin ELISA 15 minutes after injection. Read More

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https://www.ahajournals.org/doi/10.1161/STROKEAHA.118.021732
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http://dx.doi.org/10.1161/STROKEAHA.118.021732DOI Listing
May 2019
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Eudesmane Glycosides from Ambrosia artemisiifolia (Common Ragweed) as Potential Neuroprotective Agents.

J Nat Prod 2019 Apr 22. Epub 2019 Apr 22.

Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 08826 , Republic of Korea.

In Alzheimer's disease, amyloid-β (Aβ) accumulation in the brain results in neuronal cell death and is one of the major causes of dementia. Because the current therapeutic agents are not yet sufficiently effective or safe, there have been attempts to find new neuroprotective chemicals against Aβ-induced cytotoxicity. A 70% EtOH extract of whole plants of Ambrosia artemisiifolia (common ragweed) was selected after the screening of a natural extract library. Read More

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http://dx.doi.org/10.1021/acs.jnatprod.8b00841DOI Listing

Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease.

JAMA Neurol 2019 Apr 22. Epub 2019 Apr 22.

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Importance: Plasma neurofilament light (NfL) has been suggested as a noninvasive biomarker to monitor neurodegeneration in Alzheimer disease (AD), but studies are lacking.

Objective: To examine whether longitudinal plasma NfL levels are associated with other hallmarks of AD.

Design, Setting, And Participants: This North American cohort study used data from 1583 individuals in the multicenter Alzheimer's Disease Neuroimaging Initiative study from September 7, 2005, through June 16, 2016. Read More

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http://dx.doi.org/10.1001/jamaneurol.2019.0765DOI Listing

PPAR-δ Activation Ameliorates Diabetes-Induced Cognitive Dysfunction by Modulating Integrin-linked Kinase and AMPA Receptor Function.

J Am Coll Nutr 2019 Apr 22:1-10. Epub 2019 Apr 22.

a Department of Drug Discovery and Development, Harrison School of Pharmacy , Auburn University , Auburn , Alabama , USA.

An estimated 9% of the American population experiences type II diabetes mellitus (T2DM) due to diet or genetic predisposition. Recent reports indicate that patients with T2DM are at increased risk for cognitive dysfunctions, as observed in conditions like Alzheimer's disease (AD). In addition, AD is the leading cause of dementia, highlighting the urgency of developing novel therapeutic targets for T2DM-induced cognitive deficits. Read More

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http://dx.doi.org/10.1080/07315724.2019.1598307DOI Listing

Microglia in the Neurovascular Unit: Blood-Brain Barrier-microglia Interactions After Central Nervous System Disorders.

Neuroscience 2019 May 6;405:55-67. Epub 2018 Jul 6.

Faculty of Biology, Medicine and Health, AV Hill Building, The University of Manchester, United Kingdom. Electronic address:

Over the past few decades, microglial cells have been regarded as the main executor of inflammation after acute and chronic central nervous system (CNS) disorders, responding rapidly to exogenous stimuli during acute trauma or infections, or signals released by cells undergoing cell death during conditions such as stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Barriers of the nervous system, and in particular the blood-brain barrier (BBB), play a key role in the normal physiological and cognitive functions of the brain. Being at the interface between the central and peripheral compartment, the BBB is regarded as a sensor of homeostasis, and any disruption within the brain or the systemic compartment triggers BBB dysfunction and neuroinflammation, both contributing to the pathogenesis of cerebrovascular disease. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2018.06.046DOI Listing

Recalibrating the Existence of New Neurons in Adult Brain.

ACS Chem Neurosci 2019 Apr 22. Epub 2019 Apr 22.

CSIR-Indian Institute of Chemical Biology (CSIR-IICB) , Kolkata 700032 , India.

New neurons were shown to born throughout adulthood, a process known as neurogenesis. Last year, the human hippocampal neurogenesis field was flipped on its head by a paper in Nature from Sorrells et al. questioning the presence of human hippocampal neurogenesis during adulthood ( Sorrells, S. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.9b00196
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http://dx.doi.org/10.1021/acschemneuro.9b00196DOI Listing
April 2019
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Associations between sleep duration and cognitive impairment in mild cognitive impairment.

J Sleep Res 2019 Apr 21:e12864. Epub 2019 Apr 21.

Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, Crete, Greece.

The prevalence of mild cognitive impairment (MCI) increases among elderly people and is associated with a high risk of dementia. Identifying factors that may contribute to the progress of MCI to dementia is critical. The objective of this study was to examine the association of objective sleep with cognitive performance in MCI patients. Read More

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http://dx.doi.org/10.1111/jsr.12864DOI Listing

Structural correlates of attention dysfunction in Lewy body dementia and Alzheimer's disease: an ex-Gaussian analysis.

J Neurol 2019 Apr 21. Epub 2019 Apr 21.

Institute of Neuroscience, Newcastle University, Biomedical Research Building 3rd Floor, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.

Background: Lewy body dementia (LBD) and Alzheimer's disease (AD) are common forms of degenerative dementia. While they are characterized by different clinical profiles, attentional deficits are a common feature. The objective of this study was to investigate how attentional problems in LBD and AD differentially affect different aspects of reaction time performance and to identify possible structural neural correlates. Read More

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http://dx.doi.org/10.1007/s00415-019-09323-yDOI Listing

Neurodegenerative Disease-Related Proteins within the Epidermal Layer of the Human Skin.

J Alzheimers Dis 2019 Apr 15. Epub 2019 Apr 15.

Department of Pharmacology & Therapeutics, Life Sciences Complex, McGill University, Montreal, Quebec, Canada.

There is increasing evidence suggesting that amyloidogenic proteins might form deposits in non-neuronal tissues in neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. However, the detection of these aggregation-prone proteins within the human skin has been controversial. Using immunohistochemistry (IHC) and mass spectrometry tissue imaging (MALDI-MSI), fresh frozen human skin samples were analyzed for the expression and localization of neurodegenerative disease-related proteins. Read More

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http://dx.doi.org/10.3233/JAD-181191DOI Listing

Recruitment of Older Veterans with Diabetes Risk for Alzheimer's Disease for a Randomized Clinical Trial of Computerized Cognitive Training.

J Alzheimers Dis 2019 Apr 15. Epub 2019 Apr 15.

James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA.

Background: Type 2 diabetes mellitus (T2DM) is prevalent in the general United States population, and in the veteran population. T2DM has consistently been linked to increased risk for cognitive impairment, dementia, and Alzheimer's disease. Computerized cognitive training (CCT) is practical and inexpensive cognitive interventions that is an alternative to medication. Read More

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http://dx.doi.org/10.3233/JAD-180952DOI Listing

Tau Protein and Zebrafish Models for Tau-Induced Neurodegeneration.

J Alzheimers Dis 2019 Apr 15. Epub 2019 Apr 15.

Clinical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.

Tauopathies are a specific type of slow and progressive neurodegeneration, which involves intracellular deposition of fibrillar material composed of abnormal hyperphosphorylation of the microtubule associated protein (MAP) tau. Despite many years of intensive research, our understanding of the molecular events that lead to neurodegeneration is far from complete. No effective therapeutic treatments have been defined, and questions surround the validity and utility of existing animal models. Read More

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http://dx.doi.org/10.3233/JAD-180917DOI Listing

Burden of Neurodegenerative Diseases in the Eastern Mediterranean Region, 1990-2016: Findings from the Global Burden of Disease 2016 Study.

Eur J Neurol 2019 Apr 21. Epub 2019 Apr 21.

Department of Community Medicine, Preventive Medicine and Public Health Research Center, Iran University of Medical Sciences, Tehran, Iran.

Background And Purpose: The Eastern Mediterranean Region (EMR) is experiencing a demographic shift towards rapid ageing at a time of political unrest. We aimed to estimate the burden of neurodegenerative disorders, and its relationship with sociodemographic indicators (SDI) in the EMR countries from 1990 to 2016.

Methods: Using data from the Global Burden of Disease (GBD) 2016 study, we calculated country-specific trends for prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for Alzheimer's disease/other dementias and Parkinson's disease in the EMR during 1990-2016. Read More

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http://dx.doi.org/10.1111/ene.13972DOI Listing

Lycopene protects against t-BHP-induced neuronal oxidative damage and apoptosis via activation of the PI3K/Akt pathway.

Mol Biol Rep 2019 Apr 20. Epub 2019 Apr 20.

Department of Pathophysiology, Institute of Brain Science Research, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China.

Oxidative stress is a key factor of and closely implicated in the pathogenesis of Alzheimer's disease (AD). We herein used tert-butyl hydroperoxide (t-BHP) to induce oxidative stress and mimic oxidative neurotoxicity in vitro. Lycopene is a natural antioxidant that has a strong ability to eliminate free radicals and shows effective protection in some neurodegenerative disease models. Read More

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http://link.springer.com/10.1007/s11033-019-04801-y
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http://dx.doi.org/10.1007/s11033-019-04801-yDOI Listing
April 2019
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Regulation of Neprilysin Activity and Cognitive Functions in Rats After Prenatal Hypoxia.

Neurochem Res 2019 Apr 20. Epub 2019 Apr 20.

I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez av, St. Petersburg, Russia, 194223.

The amyloid-degrading enzyme neprilysin (NEP) is one of the therapeutic targets in prevention and treatment of Alzheimer's disease (AD). As we have shown previously NEP expression in rat parietal cortex (Cx) and hippocampus (Hip) decreases with age and is also significantly reduced after prenatal hypoxia. Following the paradigms for enhancement of NEP expression and activity developed in cell culture, we analysed the efficacy of various compounds able to upregulate NEP using our model of prenatal hypoxia in rats. Read More

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http://link.springer.com/10.1007/s11064-019-02796-3
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http://dx.doi.org/10.1007/s11064-019-02796-3DOI Listing
April 2019
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Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer's disease.

Acta Neuropathol 2019 Apr 20. Epub 2019 Apr 20.

Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, 221 84, Lund, Sweden.

Alzheimer's disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer's disease) mice and found specifically expressed in microglia associated with Aβ plaques. Read More

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http://dx.doi.org/10.1007/s00401-019-02013-zDOI Listing

NEAT1 regulates neuroglial cell mediating Aβ clearance via the epigenetic regulation of endocytosis-related genes expression.

Cell Mol Life Sci 2019 Apr 20. Epub 2019 Apr 20.

School of Life Sciences, Tsinghua University, Beijing, 100084, China.

The accumulation of intracellular β-amyloid peptide (Aβ) is important pathological characteristic of Alzheimer's disease (AD). However, the exact underlying molecular mechanism remains to be elucidated. Here, we reported that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), a long n on-coding RNA, exhibits repressed expression in the early stage of AD and its down-regulation declines neuroglial cell mediating Aβ clearance via inhibiting expression of endocytosis-related genes. Read More

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http://dx.doi.org/10.1007/s00018-019-03074-9DOI Listing

Inhibition of MEK5 suppresses TDP-43 toxicity via the mTOR-independent activation of the autophagy-lysosome pathway.

Biochem Biophys Res Commun 2019 Apr 17. Epub 2019 Apr 17.

Korea Brain Research Institute, Department of Neural Development and Disease, 61, Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea. Electronic address:

The most prominent hallmarks of many neurodegenerative diseases are the accumulation of misfolded protein aggregates and the death of certain neuronal populations. Autophagy is the major intracellular mechanism that degrades protein aggregates and damaged cellular components. Many studies have reported that the dysfunction of autophagy is associated with several neurodegenerative diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.04.088DOI Listing

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;128:39-49. 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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https://www.mdpi.com/1420-3049/24/8/1540
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http://dx.doi.org/10.3390/molecules24081540DOI Listing
April 2019
2 Reads

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
1 Read

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
1 Read

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
4 Reads

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
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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
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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
3 Reads

Sex-specific neurogenic deficits and neurocognitive disorders in middle-aged HIV-1 Tg26 transgenic mice.

Brain Behav Immun 2019 Apr 16. Epub 2019 Apr 16.

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
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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
3 Reads

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