163,411 results match your criteria Alzheimer's & dementia Amsterdam Netherlands[Journal]


A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders.

Planta Med 2020 Jul 14. Epub 2020 Jul 14.

Division of Mycobiology and Neurodegenerative Disease Research, Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, India.

According to the World Health Organization, neurological and neurodegenerative diseases are highly debilitating and pose the greatest threats to public health. Diseases of the nervous system are caused by a particular pathological process that negatively affects the central and peripheral nervous systems. These diseases also lead to the loss of neuronal cell function, which causes alterations in the nervous system structure, resulting in the degeneration or death of nerve cells throughout the body. Read More

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http://dx.doi.org/10.1055/a-1177-4834DOI Listing

Calbindin-D, parvalbumin, and calretinin in young and aged human locus coeruleus.

Neurobiol Aging 2020 Jun 15;94:243-249. Epub 2020 Jun 15.

Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address:

Certain neuronal populations, including basal forebrain cholinergic neurons (BFCN) and noradrenergic neurons of the locus coeruleus (LC), are selectively vulnerable to pathology and loss early in the course of aging and Alzheimer's disease (AD). Human BFCN show substantial loss of the calcium-binding protein (CBP), calbindin-D (CB), during normal aging, which is associated with formation of neurofibrillary tangles and BFCN loss in AD. Here we determined if, similar to the BFCN, LC neurons contain CB or the other 2 ubiquitous CBPs parvalbumin and calretinin, and whether these proteins display an age-related loss from LC neurons. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.06.006DOI Listing

Gray matter changes related to microglial activation in Alzheimer's disease.

Neurobiol Aging 2020 Jun 17;94:236-242. Epub 2020 Jun 17.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Neuroinflammation is increasingly recognized as playing a key pathogenetic role in Alzheimer's disease (AD). We examined the relationship between in vivo neuroinflammation and gray matter (GM) changes. Twenty-eight subjects with clinically probable AD (n = 14) and amyloid-positive mild cognitive impairment (n = 14) (age 71. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.06.010DOI Listing

Design of peptide-based inhibitor agent against amyloid-β aggregation: Molecular docking, synthesis and in vitro evaluation.

Bioorg Chem 2020 Jun 30;102:104050. Epub 2020 Jun 30.

Department of Mechanical Engineering, Sharif University of Technology, Tehran, Iran. Electronic address:

Formation of the amyloid beta (Aβ) peptide aggregations represents an indispensable role in appearing and progression of Alzheimer disease. β-sheet breaker peptides can be designed and modified with different amino acids in order to improve biological properties and binding affinity to the amyloid beta peptide. In the present study, three peptide sequences were designed based on the hopeful results of LIAIMA peptide and molecular docking studies were carried out onto the monomer and fibril structure of amyloid beta peptide using AutoDock Vina software. Read More

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http://dx.doi.org/10.1016/j.bioorg.2020.104050DOI Listing

The role of glia in protein aggregation.

Neurobiol Dis 2020 Jul 11:105015. Epub 2020 Jul 11.

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Protein aggregation diseases involve intracellular accumulation or extracellular deposition of certain protein species in neuronal or glial cells, leading to neurodegeneration and shortened lifespan. Prime examples include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), which are affected by overlapping or specific aggregation-prone proteins. Mounting evidence suggests that dysfunctional glial cells may be major drivers for some diseases, and when they are not causal factors, they could still significantly exacerbate or alleviate disease progression by playing a plethora of detrimental or beneficial roles. Read More

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http://dx.doi.org/10.1016/j.nbd.2020.105015DOI Listing

Cross-sectional and prospective associations between cerebral cortical thickness and frailty in older adults.

Exp Gerontol 2020 Jul 11:111018. Epub 2020 Jul 11.

Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital (CHU Toulouse), Toulouse, France; UPS/Inserm UMR1027, University of Toulouse III, Toulouse, France.

Background: Several neurodegenerative markers measured by magnetic resonance imaging (MRI) have shown to be related with frailty. While most studies have focused on surrogates of cerebral vascular damage such as increased white matter lesions, the associations between cortical atrophy and frailty were less often investigated.

Objectives: To investigate the cross-sectional and prospective associations between cortical thickness and frailty evolution in older adults. Read More

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http://dx.doi.org/10.1016/j.exger.2020.111018DOI Listing

Gaussian Discriminative Component Analysis for Early Detection of Alzheimer's Disease: A Supervised Dimensionality Reduction Algorithm.

J Neurosci Methods 2020 Jul 11:108856. Epub 2020 Jul 11.

Department of Electrical and Computer Engineering, Florida International University, Miami, FL, USA; 1Florida Alzheimer's Disease Research Center (ADRC), University of Florida, Gainesville, FL, USA. Electronic address:

Background: Using multiple modalities of biomarkers, several machine leaning-based approaches have been proposed to characterize patterns of structural, functional and metabolic differences discernible from multimodal neuroimaging data for Alzheimer's disease (AD). Current investigations report several studies using binary classification often augmented with local feature selection methods, while fewer other studies address the challenging problem of multiclass classification.

New Method: To assess the merits of each of these research directions, this study introduces a supervised Gaussian discriminative component analysis (GDCA) algorithm, which can effectively delineate subtle changes of early mild cognitive impairment (EMCI) group in relation to the cognitively normal control (CN) group. Read More

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http://dx.doi.org/10.1016/j.jneumeth.2020.108856DOI Listing

Quinolactacin Biosynthesis Involves NRPSs Catalyzed Dieckmann Condensation to Form the Quinolone-γ-lactam Hybrid.

Angew Chem Int Ed Engl 2020 Jul 14. Epub 2020 Jul 14.

Rice University, Chemical and Biomolecular Engineering, Rice University - BRC, 6100 main st, 77005, Houston, UNITED STATES.

Quinolactacins are novel fungal alkaloids that feature a quinolone- γ -lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease. Here, we report the identification of the quinolactacin A2 biosynthetic gene cluster and elucidate the enzymatic basis for the formation of the quinolone- γ -lactam structure. We reveal an unusual β -keto acid ( N -methyl-2-aminobenzoylacetate) precursor that is derived from the primary metabolite L-kynurenine via methylation, oxidative decarboxylation and amide hydrolysis reactions. Read More

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http://dx.doi.org/10.1002/anie.202005770DOI Listing

Artificial Intelligence for Caregivers of Persons with Alzheimer's Disease and Related Dementias: A Systematic Literature Review.

JMIR Med Inform 2020 Jun 21. Epub 2020 Jun 21.

Department of Neurology, The University of Texas at Austin Dell Medical School, Austin, US.

Background: Artificial intelligence (AI) has great potential for improving the care of persons with Alzheimer's disease and related dementias (ADRD) and the quality of life of their family caregivers. To date, however, systematic review of the literature on the impact of AI on ADRD management has been lacking.

Objective: To (1) identify and examine literature on AI that provides information to facilitate ADRD management by caregivers of individuals diagnosed with ADRD and (2) identify gaps in the literature that suggest future directions for research. Read More

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http://dx.doi.org/10.2196/18189DOI Listing

infection may contribute to systemic and intracerebral amyloid-beta: implications for Alzheimer's disease onset.

Expert Rev Anti Infect Ther 2020 Jul 14:1-4. Epub 2020 Jul 14.

Brain and Behavior Centre, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire , Preston, UK.

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http://dx.doi.org/10.1080/14787210.2020.1792292DOI Listing

Tracking Internal and Global Diffusive Dynamics During Protein Aggregation by High-Resolution Neutron Spectroscopy.

J Phys Chem Lett 2020 Jul 14. Epub 2020 Jul 14.

Proteins can misfold and form either amorphous or organized aggregates with different morphologies and features. Aggregates of amyloid nature are pathological hallmarks in so-called protein conformational diseases, including Alzheimer's and Parkinson's. Evidence prevails that the transient early phases of the reaction determine the aggregate morphology and toxicity. Read More

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http://dx.doi.org/10.1021/acs.jpclett.0c01530DOI Listing

A Novel Curcumin-Diethyl Fumarate Hybrid as Dualistic GSK-3β Inhibitor/Nrf2 Inducer for the Treatment of Parkinson's Disease.

ACS Chem Neurosci 2020 Jul 14. Epub 2020 Jul 14.

Common co-pathogenic factors, including oxidative stress and neuroinflammation, are found to play a vital role in the development of neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Nowadays, owing to the multifactorial character of the diseases, no effective therapies are available, thus underlying the need for new strategies. Overexpression of the enzyme GSK-3β and downregulation of Nrf2/ARE pathway are responsible for a decrease in antioxidant defence effects. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00363DOI Listing

Calcium Channel Blockers: A Possible Potential Therapeutic Strategy for the Treatment of Alzheimer's Dementia Patients with SARS-CoV-2 Infection.

ACS Chem Neurosci 2020 Jul 14. Epub 2020 Jul 14.

Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Cottingham Road, HU6 7RX Hull, United Kingdom.

Studies have shown that the calcium ion (Ca) plays important roles both in Alzheimer's dementia and SARS-CoV S-mediated fusion to host cell entry. An elevated level of intracellular calcium causes neuronal dysfunction, cell death, and apoptosis. Dysregulation of calcium has also been shown to increase the production of amyloid beta (Aβ) protein, the hallmark of Alzheimer's dementia. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00391DOI Listing

Microglial CX3CR1 production increases in Alzheimer's disease and is regulated by noradrenaline.

Glia 2020 Jul 14. Epub 2020 Jul 14.

Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain.

The loss of noradrenergic neurons and subsequent reduction of brain noradrenaline (NA) levels are associated with the progression of Alzheimer's disease (AD). This seems to be due mainly to the ability of NA to reduce the activation of microglial cells. We previously observed that NA induces the production of the chemokine Fractalkine/CX3CL1 in neurons. Read More

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http://dx.doi.org/10.1002/glia.23885DOI Listing

Non-invasive optical imaging of retinal Aβ plaques using curcumin loaded polymeric micelles in APP/PS1 transgenic mice for the diagnosis of Alzheimer's disease.

J Mater Chem B 2020 Jul 14. Epub 2020 Jul 14.

Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. and Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Alzheimer's disease (AD) is a neurodegenerative disease clinically characterized by impaired memory and progressive cognitive decline. Despite the advances in AD research, an effective method to timely diagnose AD has remained elusive, and until now, most AD patients receive the available symptomatic treatments late. Although the pathological hallmarks of AD have been traditionally described in the brain, recent studies have shown similar pathological changes in the retina which is developmentally an extension of the forebrain. Read More

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http://dx.doi.org/10.1039/d0tb01101kDOI Listing

Treatment of Neuroblastoma Cells with Inhibitors of Protein Disulfide Isomerase Upregulates NQO1 Activity.

Authors:
Dennis Özcelik

Chem Res Toxicol 2020 Jul 14. Epub 2020 Jul 14.

Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.

Hallmarks of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease include oxidative stress, accumulation of unfolded proteins, and neuronal cell death. One key player in maintaining redox homeostasis and oxidative protein folding is the protein disulfide isomerase (PDI). PDI has been the focus of drug discovery studies in neurodegenerative diseases, which have reported, paradoxically, that PDI inhibition is neuroprotective in cellular disease models. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.0c00101DOI Listing

Connectome Signatures of Hyperexcitation in Cognitively Intact Middle-Aged Female APOE-ε4 Carriers.

Cereb Cortex 2020 Jul 14. Epub 2020 Jul 14.

Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.

Synaptic dysfunction is hypothesized to be one of the earliest brain changes in Alzheimer's disease, leading to "hyperexcitability" in neuronal circuits. In this study, we evaluated a novel hyperexcitation indicator (HI) for each brain region using a hybrid resting-state structural connectome to probe connectome-level excitation-inhibition balance in cognitively intact middle-aged apolipoprotein E (APOE) ε4 carriers with noncarriers (16 male/22 female in each group). Regression with three-way interactions (sex, age, and APOE-ε4 carrier status) to assess the effect of APOE-ε4 on excitation-inhibition balance within each sex and across an age range of 40-60 years yielded a significant shift toward higher HI in female carriers compared with noncarriers (beginning at 50 years). Read More

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http://dx.doi.org/10.1093/cercor/bhaa190DOI Listing

Interaction between Alcohol Consumption and Apolipoprotein E (ApoE) Genotype with Cognition in Middle-Aged Men.

J Int Neuropsychol Soc 2020 Jul 14:1-13. Epub 2020 Jul 14.

Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

Objective: Heavy alcohol consumption is associated with poorer cognitive function in older adults. Although understudied in middle-aged adults, the relationship between alcohol and cognition may also be influenced by genetics such as the apolipoprotein (ApoE) ε4 allele, a risk factor for Alzheimer's disease. We examined the relationship between alcohol consumption, ApoE genotype, and cognition in middle-aged adults and hypothesized that light and/or moderate drinkers (≤2 drinks per day) would show better cognitive performance than heavy drinkers or non-drinkers. Read More

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http://dx.doi.org/10.1017/S1355617720000570DOI Listing

Social Cognition: patterns of impairments in mild and moderate Alzheimer's Disease.

Int J Geriatr Psychiatry 2020 Jul 14. Epub 2020 Jul 14.

Center for Alzheimer's disease, Institute of Psychiatry, Federal University of Rio de Janeiro, RJ, Brazil.

Objective: Social cognition (SC) deficits in Alzheimer Disease (AD) are commonly associated with the progression of the disease, and mainly as a result of global cognition deterioration. We aimed to investigate the relationship between SC, global cognition, and other clinical variables in mild and moderate people with AD and their caregivers. We also investigated the differences between self-reported SC and family caregivers' ratings of SC. Read More

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http://dx.doi.org/10.1002/gps.5379DOI Listing

Normal pressure hydrocephalus associated with Alzheimer' disease.

Ann Neurol 2020 Jul 13. Epub 2020 Jul 13.

Centre for Neurology and Neuropsychiatry, LVR-Klinikum Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

Objective: To investigate if neurodegenerative biomarkers in cerebro-spinal fluid (CSF) diffferentiate patients with suspected normal pressure hydrocephalus (NPH) who respond to CSF drainage from patients who do not respond.

Methods: Data of 62 consecutive patients who presented with MRI-changes indicative of NPH were studied with regard to cognitive and gait functions before and after drainage of 40-50 ml CSF. Additionally, S100, NSE, ß-amyloid protein, tau-protein, phospho-tau were determined in CSF. Read More

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http://dx.doi.org/10.1002/ana.25847DOI Listing

Microglia mediated neuroinflammation - signaling regulation and therapeutic considerations with special reference to some natural compounds.

Histol Histopathol 2020 Jul 14:18239. Epub 2020 Jul 14.

Technology Transfer Center, Kunming Medical University, Kunming, China.

Neuroinflammation plays a central role in multiple neurodegenerative diseases and neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemic injury etc. In this connection, microglia, the key players in the central nervous system, mediate the inflammatory response process. In brain injuries, activated microglia can clear the cellular debris and invading pathogens and release neurotrophic factors; however, prolonged microglia activation may cause neuronal death through excessive release of inflammatory mediators. Read More

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http://dx.doi.org/10.14670/HH-18-239DOI Listing

Plasma Protein Panels for Mild Cognitive Impairment Among Elderly Chinese Individuals with Different Educational Backgrounds.

J Mol Neurosci 2020 Jul 13. Epub 2020 Jul 13.

Wuxi Mental Health Center, Nanjing Medical University, No.156 Qianrong Road, Wuxi, Jiangsu Province, China.

To explore plasma protein panels as potential biomarkers to screen for mild cognitive impairment (MCI) among elderly Chinese individuals with different educational backgrounds. Forty-four illiterate, 36 lower education (1-6 years), and 55 higher education (7 years or more) elderly individuals were included in the present study. Among all subjects, 67 were healthy individuals and 68 were diagnosed with MCI. Read More

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http://dx.doi.org/10.1007/s12031-020-01659-9DOI Listing

RVG29-Functionalized Lipid Nanoparticles for Quercetin Brain Delivery and Alzheimer's Disease.

Pharm Res 2020 Jul 13;37(7):139. Epub 2020 Jul 13.

LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313, Porto, Portugal.

Purpose: Lipid nanoparticles (SLN and NLC) were functionalized with the RVG29 peptide in order to target the brain and increase the neuronal uptake through the nicotinic acetylcholine receptors. These nanosystems were loaded with quercetin to take advantage of its neuroprotective properties mainly for Alzheimer's disease.

Methods: The functionalization of nanoparticles with RVG29 peptide was confirmed by NMR and FTIR. Read More

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http://dx.doi.org/10.1007/s11095-020-02865-1DOI Listing

Brain sterol flux mediated by cytochrome P450 46A1 affects membrane properties and membrane-dependent processes.

Brain Commun 2020 11;2(1). Epub 2020 Apr 11.

Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH USA.

Cytochrome P450 46A1 encoded by catalyzes cholesterol 24-hydroxylation and is a CNS-specific enzyme that controls cholesterol removal and turnover in the brain. Accumulating data suggest that increases in cytochrome P450 46A1 activity in mouse models of common neurodegenerative diseases affect various, apparently unlinked biological processes and pathways. Yet, the underlying reason for these multiple enzyme activity effects is currently unknown. Read More

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http://dx.doi.org/10.1093/braincomms/fcaa043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357967PMC

The Association of Beta-Blocker Use to Cognitive Impairment among Adults with Hypertension or Cardiovascular Diseases in the United States.

Chronic Pain Manag 2020 1;4. Epub 2020 Jun 1.

Department of Pharmaceutical Systems and Policy, West Virginia University School of Pharmacy, USA.

Background: Some studies have shown that beta-blocker use is associated with better cognitive impairment. However, these studies did not control for pain. The relationship between pain and cognitive impairment has been exhaustively investigated. Read More

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http://dx.doi.org/10.29011/2576-957x.100025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357995PMC

Geng et al. reply.

Cell Res 2020 Jul 13. Epub 2020 Jul 13.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

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http://dx.doi.org/10.1038/s41422-020-0377-7DOI Listing

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer's disease-type pathology and cognitive deficits in APP/PS1 mice.

Transl Psychiatry 2020 Jul 13;10(1):230. Epub 2020 Jul 13.

Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, 400042, Chongqing, China.

Alzheimer's disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. Read More

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http://dx.doi.org/10.1038/s41398-020-00918-yDOI Listing

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development.

Signal Transduct Target Ther 2020 Jul 13;5(1):125. Epub 2020 Jul 13.

Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong, China.

Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. Read More

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http://dx.doi.org/10.1038/s41392-020-00233-4DOI Listing

Tauopathy in the young autistic brain: novel biomarker and therapeutic target.

Transl Psychiatry 2020 Jul 13;10(1):228. Epub 2020 Jul 13.

Elton Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, Israel.

Given our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer's disease brains correlating with increasing tauopathy, it is important to decipher if tauopathy is underlying brain imaging results of atrophy in ASD/ID children. We concentrated on activity-dependent neuroprotective protein (ADNP), a prevalent autism gene. The unique availability of multiple postmortem brain sections of a 7-year-old male, heterozygous for ADNP de novo mutation c. Read More

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http://dx.doi.org/10.1038/s41398-020-00904-4DOI Listing

Association of cerebrovascular reactivity and Alzheimer pathologic markers with cognitive performance.

Neurology 2020 Jul 13. Epub 2020 Jul 13.

Department of Radiology, Johns Hopkins University, School of Medicine, Baltimore, MD

Objective: To determine whether MRI-based cerebrovascular reactivity (CVR) can predict cognitive performance independent of Alzheimer's pathological markers, we studied the relationship between cognition, CVR, and CSF-derived Aâ42 and Tau in a group of elderly individuals with mixed Alzheimer's and vascular cognitive impairment and dementia.

Methods: A cross-sectional study of 72 participants, aged 69±8 years, consisting of individuals with normal cognition (n=28) and cognitive impairment (n=44) (including 36 mild cognitive impairment, MCI, and 8 mild dementia). CVR was measured with hypercapnia-MRI. Read More

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http://dx.doi.org/10.1212/WNL.0000000000010133DOI Listing

Relationship between β-amyloid and structural network topology in decedents without dementia.

Neurology 2020 Jul 13. Epub 2020 Jul 13.

From the Departments of Anatomy and Neurosciences (L.E.J., M.D.S., N.B., J.J.G.G., L.D., W.D.J.v.d.B.), Pathology (A.J.M.R.), and Radiology and Nuclear Medicine (F.B.), Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.

Objective: To investigate the association between β-amyloid (Aβ) load and postmortem structural network topology in decedents without dementia.

Methods: Fourteen decedents (mean age at death 72.6 ± 7. Read More

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http://dx.doi.org/10.1212/WNL.0000000000009910DOI Listing

Sleep is bi-directionally modified by amyloid beta oligomers.

Elife 2020 Jul 14;9. Epub 2020 Jul 14.

Department of Cell and Developmental Biology, UCL, London, United Kingdom.

Disrupted sleep is a major feature of Alzheimer's disease (AD), often arising years before symptoms of cognitive decline. Prolonged wakefulness exacerbates the production of amyloid-beta (Aβ) species, a major driver of AD progression, suggesting that sleep loss further accelerates AD through a vicious cycle. However, the mechanisms by which Aβ affects sleep are unknown. Read More

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http://dx.doi.org/10.7554/eLife.53995DOI Listing

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer's disease as an indicator of tau phosphorylation.

Alzheimers Res Ther 2020 Jul 13;12(1):83. Epub 2020 Jul 13.

Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea.

Background: Recently, several studies suggested potential involvements of α-synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. Read More

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http://dx.doi.org/10.1186/s13195-020-00648-9DOI Listing

Deciphering cellular transcriptional alterations in Alzheimer's disease brains.

Mol Neurodegener 2020 Jul 13;15(1):38. Epub 2020 Jul 13.

Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.

Large-scale brain bulk-RNAseq studies identified molecular pathways implicated in Alzheimer's disease (AD), however these findings can be confounded by cellular composition changes in bulk-tissue. To identify cell intrinsic gene expression alterations of individual cell types, we designed a bioinformatics pipeline and analyzed three AD and control bulk-RNAseq datasets of temporal and dorsolateral prefrontal cortex from 685 brain samples. We detected cell-proportion changes in AD brains that are robustly replicable across the three independently assessed cohorts. Read More

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http://dx.doi.org/10.1186/s13024-020-00392-6DOI Listing

Recent Advances in the Development of Casein Kinase 1 Inhibitors.

Curr Med Chem 2020 Jul 13. Epub 2020 Jul 13.

Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012. China.

Background: The casein kinase 1 (CK1) family are involved in regulating many cellular processes including membrane trafficking, DNA damage repair, cytoskeleton dynamics, cytoskeleton maintenance and apoptosis. CK1 isoforms especially CK1δ and CK1ε have emerged as important therapeutic target for severe disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), familial advanced sleep phase syndrome and cancer. Due to the importance of CK1 for the pathogenesis of disorders, there are great interests in the development of CK1 inhibitors. Read More

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http://dx.doi.org/10.2174/0929867327666200713185413DOI Listing

Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD.

Cells 2020 Jul 9;9(7). Epub 2020 Jul 9.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41068, Korea.

The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer's disease (AD) pathology has not been carefully addressed. Here, we report the regulatory function of regorafenib in neuroinflammatory responses and AD-related pathology in vitro and in vivo. Read More

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http://dx.doi.org/10.3390/cells9071655DOI Listing

The Regulatory Role of IL-10 in Neurodegenerative Diseases.

Biomolecules 2020 Jul 9;10(7). Epub 2020 Jul 9.

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy.

IL-10, an immunosuppressive cytokine, is considered an important anti-inflammatory modulator of glial activation, preventing inflammation-mediated neuronal degeneration under pathological conditions. In this narrative review, we summarize recent insights about the role of IL-10 in the neurodegeneration associated with neuroinflammation, in diseases such as Multiple Sclerosis, Traumatic Brain Injury, Amyotrophic lateral sclerosis, Alzheimer's Disease, and Parkinson's Disease, focusing on the contribution of this cytokine not only in terms of protective action, but also as possibly responsible for clinical worsening. The knowledge of this double face of the same coin, regarding the biological role of the IL-10, could aid the development of targeted therapies useful for limiting neurodegenerative processes. Read More

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http://dx.doi.org/10.3390/biom10071017DOI Listing

Dual Leucine Zipper Kinase Is Constitutively Active in the Adult Mouse Brain and Has Both Stress-Induced and Homeostatic Functions.

Int J Mol Sci 2020 Jul 9;21(14). Epub 2020 Jul 9.

The Neurodegeneration Consortium, Therapeutics Discovery Division, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.

Dual leucine zipper kinase (DLK, Map3k12) is an axonal protein that governs the balance between degeneration and regeneration through its downstream effectors c-jun N-terminal kinase (JNK) and phosphorylated c-jun (p-c-Jun). In peripheral nerves DLK is generally inactive until induced by injury, after which it transmits signals to the nucleus via retrograde transport. Here we report that in contrast to this mode of regulation, in the uninjured adult mouse cerebellum, DLK constitutively drives nuclear p-c-Jun in cerebellar granule neurons, whereas in the forebrain, DLK is similarly expressed and active, but nuclear p-c-Jun is undetectable. Read More

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http://dx.doi.org/10.3390/ijms21144849DOI Listing

Synaptosome as a tool in Alzheimer's disease research.

Brain Res 2020 Jul 10:147009. Epub 2020 Jul 10.

Department of Anatomy, School of Biomedical Sciences, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.

Synapse dysfunction is an integral feature of Alzheimer's disease (AD) pathophysiology. In fact, prodromal manifestation of structural and functional deficits in synapses much prior to appearance of overt pathological hallmarks of the disease indicates that AD might be considered as a degenerative disorder of the synapses. Several research instruments and techniques have allowed us to study synaptic function and plasticity and their alterations in pathological conditions, such as AD. Read More

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http://dx.doi.org/10.1016/j.brainres.2020.147009DOI Listing

Transcriptome analysis indicates dominant effects on ribosome and mitochondrial function of a premature termination codon mutation in the zebrafish gene psen2.

PLoS One 2020 13;15(7):e0232559. Epub 2020 Jul 13.

Alzheimer's Disease Genetics Laboratory, School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.

PRESENILIN 2 (PSEN2) is one of the genes mutated in early onset familial Alzheimer's disease (EOfAD). PSEN2 shares significant amino acid sequence identity with another EOfAD-related gene PRESENILIN 1 (PSEN1), and partial functional redundancy is seen between these two genes. However, the complete range of functions of PSEN1 and PSEN2 is not yet understood. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232559PLOS

Comparison of [11C]-PBR28 binding between persons living with HIV and HIV uninfected individuals.

J Acquir Immune Defic Syndr 2020 Jul 8. Epub 2020 Jul 8.

Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110.

Objective: Despite combined antiretroviral therapy (cART), neuroinflammation may persist in persons living with HIV (PLWH) and contribute to cognitive impairment in this population. Positron emission tomography (PET) imaging targeting 18kDa translocator protein (TSPO) has been used to localize neuroinflammation. We aimed to use TSPO-PET imaging to evaluate neuroinflammation in PLWH. Read More

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http://dx.doi.org/10.1097/QAI.0000000000002435DOI Listing

Meta-analysis of Ginkgo biloba Preparation for the Treatment of Alzheimer's Disease.

Clin Neuropharmacol 2020 Jul/Aug;43(4):93-99

Department of Second Neurology, Handan First Hospital, Handan, Hebei, China.

Objective: The objective of this study was to investigate the efficacy and safety of Ginkgo biloba preparation for the treatment of Alzheimer disease (AD).

Methods: Both English (PubMed, Embase, Cochrane Library databases, and the Cochrane Controlled Trials Register) and Chinese (WanFang, Chinese Biomedical, CNKI, and VIP databases) databases were systematically and independently searched by 2 authors from their inception until July 3, 2019. All relevant studies included AD patients who were treated with Ginkgo biloba. Read More

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http://dx.doi.org/10.1097/WNF.0000000000000394DOI Listing

Thieno[2,3-b]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease.

Arch Pharm (Weinheim) 2020 Jul 13:e2000101. Epub 2020 Jul 13.

Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.

In search of safer tacrine analogs, various thieno[2,3-b]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC values of 1.55 and 0. Read More

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http://dx.doi.org/10.1002/ardp.202000101DOI Listing

Genomic Mechanisms in Alzheimer's Disease.

Brain Pathol 2020 Jul 13. Epub 2020 Jul 13.

McCance Center for Brain Health and Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

Alzheimer's disease (AD) is the most common neurodegenerative disease and, owing to its increasing prevalence, represents one of the leading public health problems in aging populations. The molecular causes underlying the onset and progression of AD are manifold and hitherto still incompletely understood. Research over nearly four decades has clearly delineated genetics to play a crucial role in AD susceptibility, likely in concert with non-genetic factors. Read More

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http://dx.doi.org/10.1111/bpa.12882DOI Listing

Network-based characterization of disease-disease relationships in terms of drugs and therapeutic targets.

Bioinformatics 2020 Jul;36(Supplement_1):i516-i524

Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan.

Motivation: Disease states are distinguished from each other in terms of differing clinical phenotypes, but characteristic molecular features are often common to various diseases. Similarities between diseases can be explained by characteristic gene expression patterns. However, most disease-disease relationships remain uncharacterized. Read More

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http://dx.doi.org/10.1093/bioinformatics/btaa439DOI Listing

Combining phenome-driven drug-target interaction prediction with patients' electronic health records-based clinical corroboration toward drug discovery.

Bioinformatics 2020 Jul;36(Supplement_1):i436-i444

Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.

Motivation: Predicting drug-target interactions (DTIs) using human phenotypic data have the potential in eliminating the translational gap between animal experiments and clinical outcomes in humans. One challenge in human phenome-driven DTI predictions is integrating and modeling diverse drug and disease phenotypic relationships. Leveraging large amounts of clinical observed phenotypes of drugs and diseases and electronic health records (EHRs) of 72 million patients, we developed a novel integrated computational drug discovery approach by seamlessly combining DTI prediction and clinical corroboration. Read More

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http://dx.doi.org/10.1093/bioinformatics/btaa451DOI Listing

Identifying diagnosis-specific genotype-phenotype associations via joint multitask sparse canonical correlation analysis and classification.

Bioinformatics 2020 Jul;36(Supplement_1):i371-i379

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Motivation: Brain imaging genetics studies the complex associations between genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). The neurodegenerative disorders usually exhibit the diversity and heterogeneity, originating from which different diagnostic groups might carry distinct imaging QTs, SNPs and their interactions. Sparse canonical correlation analysis (SCCA) is widely used to identify bi-multivariate genotype-phenotype associations. Read More

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http://dx.doi.org/10.1093/bioinformatics/btaa434DOI Listing

Alzheimer's disease risk gene induces Tau-dependent network hyperexcitability.

Elife 2020 Jul 13;9. Epub 2020 Jul 13.

Neurology, Neurobiology, University of Alabama at Birmingham, Birmingham, United States.

Genome-wide association studies identified the locus as a leading modulator of genetic risk in Alzheimer's disease (AD). One limitation in understanding 's contribution to AD is its unknown function in the brain. AD-associated variants are generally noncoding and likely change expression. Read More

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http://dx.doi.org/10.7554/eLife.57354DOI Listing

Distinctive alteration in the expression of autophagy genes in Drosophila models of amyloidopathy and tauopathy.

Ups J Med Sci 2020 Jul 11:1-9. Epub 2020 Jul 11.

Center for Molecular Protein Science, Lund University, Lund, Sweden.

Background: Alzheimer's disease (AD) is one the most common types of dementia. Plaques of amyloid beta and neurofibrillary tangles of tau are two major hallmarks of AD. Metabolism of these two proteins, in part, depends on autophagy pathways. Read More

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http://dx.doi.org/10.1080/03009734.2020.1785063DOI Listing

Discontinued disease-modifying therapies for Alzheimer's disease: status and future perspectives.

Expert Opin Investig Drugs 2020 Jul 11. Epub 2020 Jul 11.

Unit of Epidemiological Research on Aging "GreatAGE Study", National Institute of Gastroenterology and Research Hospital IRCCS "S. De Bellis" Castellana Grotte , Bari, Italy.

Introduction: Alzheimer's disease (AD) is the main cause of dementia and represents a huge burden for patients, carers and healthcare systems. Extensive efforts for over twenty years have failed to find effective disease-modifying drugs. Although amyloid-β (Aβ) accumulation in the brain predicts cognitive decline, effective reduction of plaque load by numerous drug candidates has not yielded significant clinical benefits. Read More

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http://dx.doi.org/10.1080/13543784.2020.1795127DOI Listing