148,756 results match your criteria Alzheimer's & dementia New York N. Y.[Journal]


Streptozotocin causes acute responses on hippocampal S100B and BDNF proteins linked to glucose metabolism alterations.

Neurochem Int 2019 Apr 19. Epub 2019 Apr 19.

Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Streptozotocin (STZ) is a glucosamine-nitrosourea commonly used to induce long-lasting models of diabetes mellitus and Alzheimer's disease. Direct toxicity of STZ on the pancreas and kidneys has been well characterized, but the acute effect of this compound on brain tissue has received less attention. Herein, we investigated the acute and direct toxicity of STZ on fresh hippocampal slices, measuring changes in BDNF and S100B secretion (two widely-used peripheral markers of brain injury), as well as glucose metabolism. Read More

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http://dx.doi.org/10.1016/j.neuint.2019.04.013DOI Listing

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
1 Read

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

Fluorescence chemicals to detect insoluble and soluble amyloid-β aggregates.

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

Misfolded amyloid-β (Aβ) is the key biomarker of Alzheimer disease (AD), and discoveries of fluorescence chemicals visualizing such Aβ aggregates in the brain have made major contributions in postmortem and antemortem diagnosis of the disorder. Insoluble senile plaques of Aβ in brain tissues are commonly stained by thioflavin and congo red dyes and observed through microscopy, while those in living patient brains are detected by radioisotope-labeled fluorescence chemicals for positron emission tomography. Clinical evidences strongly support the view that plaques are well-associated with the onset but not with the progression of AD. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00199DOI Listing

A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia.

Brain 2019 Apr 22. Epub 2019 Apr 22.

Avid Radiopharmaceuticals, Philadelphia, PA, USA.

The advent of tau-targeted PET tracers such as flortaucipir (18F) (flortaucipir, also known as 18F-AV-1451 or 18F-T807) have made it possible to investigate the sequence of development of tau in relationship to age, amyloid-β, and to the development of cognitive impairment due to Alzheimer's disease. Here we report a multicentre longitudinal evaluation of the relationships between baseline tau, tau change and cognitive change, using flortaucipir PET imaging. A total of 202 participants 50 years old or older, including 57 cognitively normal subjects, 97 clinically defined mild cognitive impairment and 48 possible or probable Alzheimer's disease dementia patients, received flortaucipir PET scans of 20 min in duration beginning 80 min after intravenous administration of 370 MBq flortaucipir (18F). Read More

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http://dx.doi.org/10.1093/brain/awz090DOI Listing

Association of Cortical β-Amyloid Protein in the Absence of Insoluble Deposits With Alzheimer Disease.

JAMA Neurol 2019 Apr 22. Epub 2019 Apr 22.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.

Importance: β-Amyloid deposits are a pathologic hallmark of Alzheimer disease (AD). However, the extent to which cortical β-amyloid protein in the absence of insoluble deposits is associated with classic features of AD appear to be unknown.

Objective: To examine the associations of cortical β-amyloid protein in the absence of insoluble deposits with cognitive decline, neurofibrillary tangles, other age-associated neuropathologic conditions, and APOE. Read More

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http://dx.doi.org/10.1001/jamaneurol.2019.0834DOI 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

Errorless Learning as a method of neuropsychological rehabilitation of individuals suffering from dementia in the course of Alzheimer's disease.

Psychiatr Pol 2019 Feb 28;53(1):117-127. Epub 2019 Feb 28.

Uniwersytet Medyczny we Wrocławiu, Katedra Psychiatrii.

The following article discusses the possibility of applying a rehabilitation strategy known as Errorless Learning (EL) in patients suffering from Alzheimer's disease (AD). The authors present the issue in the context of the knowledge on the effectiveness of administering neuropsychological interventions in patients with AD. The history of the EL method development is presented as well as techniques used in its domain. Read More

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http://dx.doi.org/10.12740/PP/81104DOI Listing
February 2019

Characterizing Anatomical Variability And Alzheimer's Disease Related Cortical Thinning in the Medial Temporal Lobe Using Graph-Based Groupwise Registration And Point Set Geodesic Shooting.

Shape Med Imaging (2018) 2018 Sep 23;11167:28-37. Epub 2018 Nov 23.

Penn Image Computing and Science Laboratory (PICSL), Department of Radiology, University of Pennsylvania, Philadelphia, USA.

The perirhinal cortex (PRC) is a site of early neurofibrillary tangle (NFT) pathology in Alzheimer's disease (AD). Subtle morphological changes in the PRC have been reported in MRI studies of early AD, which has significance for clinical trials targeting preclinical AD. However, the PRC exhibits considerable anatomical variability with multiple described in the neuroanatomy literature. Read More

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http://dx.doi.org/10.1007/978-3-030-04747-4_3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469499PMC
September 2018

Amyloid Peptide 1-42 Induces Integrin IIb3 Activation, Platelet Adhesion, and Thrombus Formation in a NADPH Oxidase-Dependent Manner.

Oxid Med Cell Longev 2019 14;2019:1050476. Epub 2019 Mar 14.

Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, UK.

The progression of Alzheimer's dementia is associated with neurovasculature impairment, which includes inflammation, microthromboses, and reduced cerebral blood flow. Here, we investigate the effects of amyloid peptides on the function of platelets, the cells driving haemostasis. Amyloid peptide 1-42 (A1-42), A1-40, and A25-35 were tested in static adhesion experiments, and it was found that platelets preferentially adhere to A1-42 compared to other A peptides. Read More

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http://dx.doi.org/10.1155/2019/1050476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441506PMC

Proteins as the Molecular Markers of Male Fertility.

J Hum Reprod Sci 2019 Jan-Mar;12(1):19-23

Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, India.

Proteins play a key role in many functions such as metabolic activity, differentiation, as cargos, and cell fate regulators. It is necessary to know about the proteins involved in male fertility to develop remedies for the treatment of male infertility. However, the role of the proteins is not limited to particular aspect in the biological systems. Read More

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http://www.jhrsonline.org/text.asp?2019/12/1/19/255785
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http://dx.doi.org/10.4103/jhrs.JHRS_9_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472198PMC
April 2019
1 Read

Storage, Degradation, and New Connectivity of Face-Related Semantic Memory in Alzheimer's Disease.

Ann Indian Acad Neurol 2019 Apr-Jun;22(2):170-174

Department of Neurology, Medical College Hospital, Kolkata, West Bengal, India.

Background: Excepting amnesia, impairment of other domains also hampers the activity of daily living in Alzheimer's disease (AD). Although prosopagnosia poses problem in interacting with other persons, it rarely causes problem during interaction with close relatives as known voice acts as cue for recognition.

Objective: In a cohort of AD, we planned to study errors in recognition, naming, and assigning relationship of close relatives, to assess the type and frequency of errors and to explain with current knowledge and hypothesis. Read More

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http://dx.doi.org/10.4103/aian.AIAN_185_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472242PMC

Alzheimer's disease.

Authors:
Richard Barnett

Lancet 2019 Apr;393(10181):1589

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http://dx.doi.org/10.1016/S0140-6736(19)30851-7DOI 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

Emerging drugs for progressive supranuclear palsy.

Expert Opin Emerg Drugs 2019 Apr 21. Epub 2019 Apr 21.

a Parkinson's disease and Movement Disorders department , Hygeia Hospital , Athens , Greece.

Introduction: Progressive supranuclear palsy (PSP) is a common cause of atypical parkinsonism and a rapidly progressive disease that greatly burdens both patients and caregivers. Drugs with disease-modifying potential, targeting mechanisms implicated in the disease's pathogenesis are currently tested in Phase 1 and 2 trials. If proven efficacious, these compounds might provide substantial benefits not only to patients with PSP, but to patients with other tauopathies as well. Read More

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http://dx.doi.org/10.1080/14728214.2019.1609450DOI 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
3 Reads

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

The Prevalence and Subtypes of Young Onset Dementia in Central Norway:\\ A Population-Based Study.

J Alzheimers Dis 2019 Apr 17. Epub 2019 Apr 17.

Department of Neuromedicine and Movement Science (INB), NTNU, Faculty of Medicine and Health Sciences, Trondheim, Norway.

Background: Young onset dementia poses several challenges for the individual, health care, and society that are not normally relevant for late onset dementia, but is little researched.

Objective: To determine the prevalence and subtypes of young onset dementia in a defined catchment area in central Norway.

Methods: The main sources of patient identification were the databases at the Department of Neurology, University Hospital of Trondheim (St. Read More

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https://www.medra.org/servlet/aliasResolver?alias=iospress&a
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http://dx.doi.org/10.3233/JAD-181223DOI Listing
April 2019
1 Read

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

A Unifying Hypothesis for Alzheimer's Disease: From Plaques to Neurodegeneration.

Trends Neurosci 2019 Apr 4. Epub 2019 Apr 4.

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

Evidence suggests that amyloid β is highly toxic to synapses in a phospho-Tau-dependent manner. Here, I present a hypothesis that links previous evidence from the first rise of amyloid β through to Tau tangles and neurodegeneration. In the immediate vicinity of plaques, concentrated soluble amyloid β occurs in equilibrium with deposited forms. Read More

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http://dx.doi.org/10.1016/j.tins.2019.03.003DOI Listing

[Effect of apolipoprotein E genotype on magnetic resonance spectrum in amnestic mild cognitive impairment and Alzheimer's disease patients].

Zhonghua Yi Xue Za Zhi 2019 Apr;99(15):1156-1161

Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.

To explore the relationship between apolipoprotein E (ApoE) gene polymorphism and hydrogen proton magnetic resonance spectroscopy ((1)H-MRS) in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment(aMCI). The cognitive function of 35 AD patients (AD group), 35 aMCI patients (aMCI group) and 36 normal controls (NC group) were evaluated by neuropsychological scales, including Mini-mental State Examination (MMSE) and Cambridge Cognitive Examination-Chinese version (CAMCOG-C). The genotypes of ApoE were analyzed by high-resolution melting assay. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0376-2491.2019.15.008DOI 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

Metal-dependent interactions of metallothionein-3 β-domain with amyloid-β peptide and related physiological implications.

J Inorg Biochem 2019 Apr 13;196:110693. Epub 2019 Apr 13.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, PR China. Electronic address:

Aberrant interactions of metal ions with amyloid-β peptide (Aβ) can potentiate Alzheimer's disease (AD) by participating in the aggregation process of Aβ and in the generation of reactive oxygen species (ROS). Metallothionein-3 (MT3), which is aberrantly expressed in AD brains, is believed to play an important role in the AD progression due to its ability of maintaining metal homeostasis and scavenging ROS. However, the related molecular mechanism is not clear. Read More

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http://dx.doi.org/10.1016/j.jinorgbio.2019.110693DOI 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

Generation of induced pluripotent stem cells (iPSCs) IRMBi002-A from an Alzheimer's disease patient carrying a D694N mutation in the APP gene.

Stem Cell Res 2019 Apr 15;37:101438. Epub 2019 Apr 15.

Institute for Regenerative Medicine and Biotherapy (IRMB), Montpellier, France; Hopital St Eloi, CHU Montpellier, 80 rue augustin Fliche, 30295 Montpellier, France. Electronic address:

Induced pluripotent stem cells (iPSC) were generated from skin fibroblasts obtained from a 58 year-old woman suffering from Alzheimer's disease and carrying a D694N mutation on Amyloid precursor protein (APP). Fibroblasts were reprogrammed into iPSC using the integration-free Sendai Virus which allows the expression of the Yamanaka factors. Verification of their pluripotency was achieved by demonstrating the expression of pluripotency markers and their differentiation potential into the three primary germ layers. Read More

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http://dx.doi.org/10.1016/j.scr.2019.101438DOI 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
1 Read

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

Regulation of neuronal microtubule dynamics by tau: Implications for tauopathies.

Int J Biol Macromol 2019 Apr 17. Epub 2019 Apr 17.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India. Electronic address:

In specialized cell types such as neurons, microtubules maintain the integrity of axons by forming stable bundles and facilitate the transport of synaptic vesicles. The cells regulate the stability and dynamics of microtubules using a diverse array of mechanisms. One of the mechanisms involves the interaction of microtubules with its associated proteins. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01418130193056
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http://dx.doi.org/10.1016/j.ijbiomac.2019.04.120DOI Listing
April 2019
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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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Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer's disease pathologies.

Proc Natl Acad Sci U S A 2019 Apr 19. Epub 2019 Apr 19.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;

BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer's disease (AD). BDNF deficiency's association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Read More

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http://dx.doi.org/10.1073/pnas.1901348116DOI Listing
April 2019
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α-Sheet secondary structure in amyloid β-peptide drives aggregation and toxicity in Alzheimer's disease.

Proc Natl Acad Sci U S A 2019 Apr 19. Epub 2019 Apr 19.

Department of Molecular Engineering, University of Washington, Seattle, WA 98195;

Alzheimer's disease (AD) is characterized by the deposition of β-sheet-rich, insoluble amyloid β-peptide (Aβ) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aβ oligomers adopt a nonstandard secondary structure, termed "α-sheet." These oligomers form in the lag phase of aggregation, when Aβ-associated cytotoxicity peaks, en route to forming nontoxic β-sheet fibrils. Read More

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http://dx.doi.org/10.1073/pnas.1820585116DOI Listing

Deep learning only by normal brain PET identify unheralded brain anomalies.

EBioMedicine 2019 Apr 16. Epub 2019 Apr 16.

Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea. Electronic address:

Background: Recent deep learning models have shown remarkable accuracy for the diagnostic classification. However, they have limitations in clinical application due to the gap between the training cohorts and real-world data. We aimed to develop a model trained only by normal brain PET data with an unsupervised manner to identify an abnormality in various disorders as imaging data of the clinical routine. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23523964193026
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http://dx.doi.org/10.1016/j.ebiom.2019.04.022DOI Listing
April 2019
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Combinatory microRNA serum signatures as classifiers of Parkinson's disease.

Parkinsonism Relat Disord 2019 Apr 11. Epub 2019 Apr 11.

Department of Biological Sciences, St. John's University, New York, NY, USA
. Electronic address:

Introduction: As current clinical diagnostic protocols for Parkinson's disease (PD) may be prone to inaccuracies there is a need to identify and validate molecular biomarkers, such as circulating microRNAs, which will complement current practices and increase diagnostic accuracy. This study identifies, verifies and validates combinatory serum microRNA signatures as diagnostic classifiers of PD across different patient cohorts.

Methods: 370 PD (drug naïve) and control serum samples from the Norwegian ParkWest study were used for identification and verification of differential microRNA levels in PD which were validated in a blind study using 64 NY Parkinsonism in UMeå (NYPUM) study serum samples and tested for specificity in 48 Dementia Study of Western Norway (DemWest) study Alzheimer's disease (AD) serum samples using miRNA-microarrays, and quantitative (q) RT-PCR. Read More

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http://dx.doi.org/10.1016/j.parkreldis.2019.04.010DOI 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
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Dopamine receptor D (DRD) polymorphisms with reduced functional potency intensify atrophy in syndrome-specific sites of frontotemporal dementia.

Neuroimage Clin 2019 Apr 10;23:101822. Epub 2019 Apr 10.

Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA.

Objective: We aimed to understand the impact of dopamine receptor D (DRD) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRDdampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101822DOI Listing