161,685 results match your criteria Alzheimer's & dementia New York N. Y.[Journal]


Slow blood-to-brain transport underlies enduring barrier dysfunction in American football players.

Brain 2020 May 28. Epub 2020 May 28.

Departments of Physiology and Cell Biology, Brain and Cognitive Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood-brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. Read More

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http://dx.doi.org/10.1093/brain/awaa140DOI Listing

Altered sulcogyral patterns of orbitofrontal cortex in patients with mild cognitive impairment.

Psychiatry Res Neuroimaging 2020 May 21;302:111108. Epub 2020 May 21.

Reward, Competition and Social Neuroscience Lab, Department of Psychology, School of Social and Behavioral Sciences, Nanjing University, Nanjing, China; Institute for Brain Sciences, Nanjing University, Nanjing, China. Electronic address:

Mild cognitive impairment (MCI) is increasingly recognized as a risk factor for Alzheimer's disease (AD). Neuroimaging studies have revealed structural abnormalities in the orbitofrontal cortex (OFC) in MCI patients, while other findings fail to report anatomical alterations. Accordingly, structural changes in this brain region amongst MCI patients has not been well characterized. Read More

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http://dx.doi.org/10.1016/j.pscychresns.2020.111108DOI Listing

The role of nitric oxide in brain disorders: Autism spectrum disorder and other psychiatric, neurological, and neurodegenerative disorders.

Redox Biol 2020 May 15;34:101567. Epub 2020 May 15.

Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address:

Nitric oxide (NO) is a multifunctional signalling molecule and a neurotransmitter that plays an important role in physiological and pathophysiological processes. In physiological conditions, NO regulates cell survival, differentiation and proliferation of neurons. It also regulates synaptic activity, plasticity and vesicle trafficking. Read More

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http://dx.doi.org/10.1016/j.redox.2020.101567DOI Listing

Age-dependent effect of APOE and polygenic component on Alzheimer's disease.

Neurobiol Aging 2020 Apr 30;93:69-77. Epub 2020 Apr 30.

UK Dementia Research Institute at Cardiff University, Cardiff, United Kingdom; UK Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom. Electronic address:

Alzheimer's disease (AD) is a devastating neurodegenerative condition with significant genetic heritability. Several genes have been implicated in the onset of AD with the apolipoprotein E (APOE) gene being the strongest single genetic risk loci. Evidence suggests that the effect of APOE alters with age during disease progression. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.04.024DOI Listing

The Application of Ferroptosis in Diseases.

Pharmacol Res 2020 May 25:104919. Epub 2020 May 25.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China. Electronic address:

Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Ferroptosis involves various biology processes, such as iron metabolism, lipid metabolism, oxidative stress and biosynthesis of nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH) and coenzyme Q10 (CoQ10). A growing body of evidence suggests that ferroptosis is associated with cancer and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and Huntington's disease). Read More

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http://dx.doi.org/10.1016/j.phrs.2020.104919DOI Listing

Collagen hydrogel confinement of Amyloid-β (Aβ) accelerates aggregation and reduces cytotoxic effects.

Acta Biomater 2020 May 25. Epub 2020 May 25.

Department of Chemical, Biochemical and Environmental Engineering, University of Maryland Baltimore County, Baltimore, Maryland, USA. Electronic address:

Alzheimer's disease (AD) is the most common form of dementia and is associated with the accumulation of amyloid-β (Aβ), a peptide whose aggregation has been associated with neurotoxicity. Drugs targeting Aβ have shown great promise in 2D in vitro models and mouse models, yet preclinical and clinical trials for AD have been highly disappointing. We propose that current in vitro culture systems for discovering and developing AD drugs have significant limitations; specifically, that Aβ aggregation is vastly different in these 2D cultures carried out on flat plastic or glass substrates vs. Read More

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http://dx.doi.org/10.1016/j.actbio.2020.05.030DOI Listing

The Use of Patient-Derived Induced Pluripotent Stem Cells for Alzheimer's Disease Modeling.

Prog Neurobiol 2020 May 25:101804. Epub 2020 May 25.

Division of Neurology, The University of British Columbia, Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. Electronic address:

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive deterioration in multiple facets of cognitive function. As average age of the population rises, AD poses a massive current and future healthcare threat. Today, there is no cure for AD nor well-established interventions to slow progression, and treatment is largely symptomatic. Read More

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http://dx.doi.org/10.1016/j.pneurobio.2020.101804DOI Listing

Neuroprotective effect of quercetin nanoparticles: A possible prophylactic and therapeutic role in alzheimer's disease.

J Chem Neuroanat 2020 May 25:101795. Epub 2020 May 25.

Department of Histology and Cell Biology, Minia University- Faculty of Medicine, Egypt.

Background: Alzheimer's disease (AD) is the most common cause of dementia in elderly. Quercetin is a well-known flavonoid with low bioavailability. Recently, quercetin nanoparticles (QNPs) has been shown to have a better bioavailability. Read More

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http://dx.doi.org/10.1016/j.jchemneu.2020.101795DOI Listing

Defining the Neural Kinome: Strategies and Opportunities for Small Molecule Drug Discovery to Target Neurodegenerative Diseases.

ACS Chem Neurosci 2020 May 28. Epub 2020 May 28.

Kinases are highly tractable drug targets that have reached unparalleled success in fields such as cancer but whose potential has not yet been realized in neuroscience. There are currently 55 approved small molecule kinase-targeting drugs, 48 of which have an anti-cancer indication. The intrinsic complexity linked to central nervous system (CNS) drug development and a lack of validated targets has hindered progress in developing kinase inhibitors for CNS disorders when compared to other therapeutic areas such as oncology. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00176DOI Listing

Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes) Ameliorates Spatial Learning and Memory Deficits in Rats with Hypercholesterolemia and Alzheimer's Disease.

Int J Med Mushrooms 2020 ;22(1):93-103

Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Hypercholesterolemia has been implicated as one of the pathomechanistic factors of Alzheimer's disease (AD), the most common neurodegenerative disorder affecting memory and learning abilities. In the present study, ameliorative effect of hot water extract (HWE) of mushroom Ganoderma lucidum to the memory and learning related behavioral performance of hypercholesterolemic and AD rats was investigated using Morris water maze (MWM). Male Wistar rats were randomly grouped into control, extract fed control, hypercholesterolemic, extract fed hypercholesterolemic, AD, and extract fed AD groups, each group containing 8 animals. Read More

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http://dx.doi.org/10.1615/IntJMedMushrooms.2020033383DOI Listing
January 2020

GSK-3β regulates the synaptic expression of NMDA receptors via phosphorylation of phosphatidylinositol 4 kinase type IIα.

Eur J Neurosci 2020 May 28. Epub 2020 May 28.

Glutamate Receptor Group, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.

Deregulation of GSK-3β is strongly implicated in a variety of serious brain conditions, such as Alzheimer disease, bipolar disorder and schizophrenia. To understand how GSK-3β becomes dysregulated in these conditions it is important to understand its physiological functions in the central nervous system. In this context, GSK-3β plays a role in the induction of NMDA receptor-dependent long-term depression (LTD) and several substrates for GSK-3β have been identified in this form of synaptic plasticity, including KLC-2, PSD-95 and tau. Read More

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http://dx.doi.org/10.1111/ejn.14841DOI Listing

Influence of human amylin on the membrane stability of rat primary hippocampal neurons.

Aging (Albany NY) 2020 May 28;12. Epub 2020 May 28.

Department of Pharmacology, Institution of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, Hebei, China.

The two most common aging-related diseases, Alzheimer's disease and type 2 diabetes mellitus, are associated with accumulation of amyloid proteins (β-amyloid and amylin, respectively). This amylin aggregation is reportedly cytotoxic to neurons. We found that aggregation of human amylin (hAmylin) induced neuronal apoptosis without obvious microglial infiltration . Read More

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http://dx.doi.org/10.18632/aging.103105DOI Listing

Time Will Tell the Utility of Biomarkers.

ACS Chem Neurosci 2020 May 28. Epub 2020 May 28.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, United States.

A biomarker, such as protein accumulation as an indicator of disease, can be used to predict disease manifestation, determine intervention, and monitor treatment efficacy. Biomarker development frequently focuses on early detection of disease as this is typically considered the only or most pressing need. However, the ideal time point for biomarker use may not always be early in disease but instead, as we will discuss, could be when enough information is available to predict the association between biomarker (protein accumulation) and disease manifestation (symptom severity, progression, prognosis). Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00238DOI Listing

Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death.

Mov Disord 2020 May 28. Epub 2020 May 28.

Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.

Background: Premutation size (55-199 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene cause fragile X-associated tremor/ataxia syndrome, but it is unclear whether smaller "gray" zone expansions of 41-54 repeats are also associated with movement disorders. The objectives of this study were to determine the association between the FMR1 gene gray zone expansions, AGG interspersions, and the presence of parkinsonism and motor and cognitive function in an elderly community-based population.

Methods: Automated FMR1 polymerase chain reaction was performed on existing samples from 2 longitudinal aging studies whose subjects agreed to brain donation. Read More

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http://dx.doi.org/10.1002/mds.28086DOI Listing

Neuron-Glia interaction: Molecular basis of Alzheimer's Disease and Applications of Neuroproteomics.

Eur J Neurosci 2020 May 28. Epub 2020 May 28.

Special centre for Molecular Medicine, Jawaharlal Nehru University, New-Delhi, India.

Neurodegenerative disorders present with progressive and irreversible degeneration of the neurons. The most common neurodegenerative disorder is Alzheimer's disease (AD) affecting 50 million people worldwide in 2017, expected to be doubled every 20 years. Primarily affected by age, AD is the cause for old-age dementia, progressive memory loss, dysfunctional thoughts, confusion, cognitive impairment and personality changes. Read More

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http://dx.doi.org/10.1111/ejn.14838DOI Listing

Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial.

JAMA Netw Open 2020 May 1;3(5):e206027. Epub 2020 May 1.

Department of Psychiatry, University Hospital Cologne, Medical Faculty, Cologne, Germany.

Importance: Apathy is a frequent neuropsychiatric symptom in dementia of Alzheimer type and negatively affects the disease course and patients' and caregivers' quality of life. Effective treatment options are needed.

Objective: To examine the efficacy and safety of the dopamine and noradrenaline reuptake inhibitor bupropion in the treatment of apathy in patients with dementia of Alzheimer type. Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2020.6027DOI Listing

Viewpoint: Impact of the Covid-19 Outbreak on the Clinical and Research Activities of Memory Clinics: An Alzheimer's Disease Center Facing the Covid-19 Crisis.

Authors:
P J Ousset B Vellas

J Prev Alzheimers Dis 2020 ;7(3):197-198

Pierre Jean Ousset, Toulouse Alzheimer's Disease Research and Clinical Center, UMR INSERM 1027, Gerontopole, Toulouse University Hospital, France,

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http://dx.doi.org/10.14283/jpad.2020.17DOI Listing
January 2020

Viewpoint: Futility Analyses in Alzheimer's Disease (AD) Clinical Trials: A Risky Business.

Authors:
P S Aisen R Raman

J Prev Alzheimers Dis 2020 ;7(3):195-196

R. Raman, Director of Biostatistics, Alzheimer's Therapeutic Research Institute (ATRI), Director, Biostatistics Unit, Alzheimer's Clinical Trials Consortium (ACTC), Keck School of Medicine of USC, University of Southern California, 9860 Mesa Rim Road, San Diego, CA 92121, USA, Phone: 858-964-0673,

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http://dx.doi.org/10.14283/jpad.2020.20DOI Listing
January 2020

Development of an UPSA Short Form for Use in Longitudinal Studies in the Early Alzheimer's Disease Spectrum.

J Prev Alzheimers Dis 2020 ;7(3):179-183

Dr. Jesus J. Gomar, Litwin-Zucker Alzheimer's Disease Center, Feinstein Institute, Manhassett, NY, USA, Email: Telephone: 516-562-0420, Fax: 516-562-0401.

Background: In individuals with only mild or very mild cognitive attenuations (i.e., so-called pre-clinical AD), performance-based measures of function may be superior to informant-based measures because of increased sensitivity, greater reliability, and fewer ceiling effects. Read More

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http://dx.doi.org/10.14283/jpad.2019.51DOI Listing
January 2020

Early Detection of Mild Cognitive Impairment (MCI) in an At-Home Setting.

J Prev Alzheimers Dis 2020 ;7(3):171-178

Marwan N. Sabbagh, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA, Tel.: (702) 483-6029; Fax: (702) 722-6584.

Emerging digital tools have the potential to enable a new generation of qualitative and quantitative assessment of cognitive performance. Moreover, the ubiquity of consumer electronics, such as smartphones and tablets, can be harnessed to support large-scale self-assessed cognitive screening with benefit to healthcare systems and consumers. A wide variety of apps, wearables, and new digital technologies are either available or in development for the detection of mild cognitive impairment (MCI), a risk factor for dementia. Read More

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http://dx.doi.org/10.14283/jpad.2020.22DOI Listing
January 2020

Early Detection of Mild Cognitive Impairment (MCI) in Primary Care.

J Prev Alzheimers Dis 2020 ;7(3):165-170

Marwan N. Sabbagh, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA, Tel.: (702) 483-6029; Fax: (702) 722-6584.

Mild cognitive impairment (MCI) is significantly misdiagnosed in the primary care setting due to multi-dimensional frictions and barriers associated with evaluating individuals' cognitive performance. To move toward large-scale cognitive screening, a global panel of clinicians and cognitive neuroscientists convened to elaborate on current challenges that hamper widespread cognitive performance assessment. This report summarizes a conceptual framework and provides guidance to clinical researchers and test developers and suppliers to inform ongoing refinement of cognitive evaluation. Read More

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http://dx.doi.org/10.14283/jpad.2020.21DOI Listing
January 2020

Rationale for Early Diagnosis of Mild Cognitive Impairment (MCI) Supported by Emerging Digital Technologies.

J Prev Alzheimers Dis 2020 ;7(3):158-164

Marwan N. Sabbagh, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA, Tel.: (702) 483-6029; Fax: (702) 722-6584.

Disease-modifying pharmacotherapies for Alzheimer's Disease (AD) are currently in late-stage clinical development; once approved, new healthcare infrastructures and services, including primary healthcare, will be necessary to accommodate a huge demand for early and large-scale detection of AD. The increasing global accessibility of digital consumer electronics has opened up new prospects for early diagnosis and management of mild cognitive impairment (MCI) with particular regard to AD. This new wave of innovation has spurred research in both academia and industry, aimed at developing and validating a new "digital generation" of tools for the assessment of the cognitive performance. Read More

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http://dx.doi.org/10.14283/jpad.2020.19DOI Listing
January 2020

Non-Amyloid Approaches to Disease Modification for Alzheimer's Disease: An EU/US CTAD Task Force Report.

J Prev Alzheimers Dis 2020 ;7(3):152-157

Serge Gauthier, McGill Center for Studies in Aging, Verdun QC, Canada,

While amyloid-targeting therapies continue to predominate in the Alzheimer's disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of alternative treatment approaches, which would include increased partnerships and collaborations, improved trial designs, and further exploration of combination therapy strategies. Read More

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http://dx.doi.org/10.14283/jpad.2020.18DOI Listing
January 2020

The Future of Anti-Amyloid Trials.

J Prev Alzheimers Dis 2020 ;7(3):146-151

P.S. Aisen, University of Southern California Alzheimer's Therapeutic Research Institute, San Diego, CA, USA,

The termination of many clinical trials of amyloid-targeting therapies for the treatment of Alzheimer's disease (AD) has had a major impact on the AD clinical research enterprise. However, positive signals in recent studies have reinvigorated support for the amyloid hypothesis and amyloid-targeting strategies. In December 2019, the EU-US Clinical Trials on Alzheimer's Disease (CTAD) Task Force met to share learnings from these studies in order to inform future trials and promote the development of effective AD treatments. Read More

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http://dx.doi.org/10.14283/jpad.2020.24DOI Listing
January 2020

Editorial: Next-Generation Alzheimer's Therapeutics: Leveraging Deep Biology.

Authors:
F M Longo S M Massa

J Prev Alzheimers Dis 2020 ;7(3):138-139

Frank M. Longo, Department of Neurology and Neurological Sciences, Stanford University, USA,

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http://dx.doi.org/10.14283/jpad.2020.30DOI Listing
January 2020

Study on myelin injury of AD mice treated with Shenzhiling oral liquid in the PI3K/Akt-mTOR pathway.

Int J Immunopathol Pharmacol 2020 Jan-Dec;34:2058738420923907

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.

Shenzhiling oral liquid (SZL) is a Traditional Chinese Medicine (TCM) compound to be approved by the China Food and Drug Administration (CFDA) (Z20120010) for the treatment of mild-to-moderate Alzheimer's disease (AD). However, its mechanism in early AD is not clear. We studied its mechanism in protecting myelin. Read More

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http://dx.doi.org/10.1177/2058738420923907DOI Listing

Does bilingualism protect against dementia? A meta-analysis.

Psychon Bull Rev 2020 May 27. Epub 2020 May 27.

Department of Psychology, Iowa State University, Ames, IA, USA.

Evidence suggests that bilingualism may contribute to neuroplasticity and cognitive reserve, allowing individuals to resist cognitive decline associated with Alzheimer's disease progression, although the idea remains controversial. Here, we argue that the reason for the discrepancy stems from conflating incidence rates of dementia and the age at which the symptoms first appear, as well as statistical and methodological issues in the study designs. To clarify the issues, we conducted a comprehensive meta-analysis on the available literature regarding bilingualism and Alzheimer's disease, including both retrospective and prospective studies, as well as age of onset and incidence rates. Read More

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http://dx.doi.org/10.3758/s13423-020-01736-5DOI Listing

Mitochondrial Dysfunction: a Potential Therapeutic Target to Treat Alzheimer's Disease.

Mol Neurobiol 2020 May 27. Epub 2020 May 27.

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.

Mitochondrial dysfunction plays a very vital role in the pathogenesis of Alzheimer's disease (AD). Several shreds of evidence have indicated that the mitochondrial function is severely compromised under AD pathogenesis. Most of the recent therapeutic strategies have been conversed to treat AD by pinpointing the pathways involved in the pathophysiology of AD. Read More

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http://dx.doi.org/10.1007/s12035-020-01945-yDOI Listing

Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer's disease.

Eur J Nucl Med Mol Imaging 2020 May 27. Epub 2020 May 27.

Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer's disease (AD), by using a single dynamic [F]flortaucipir positron emission tomography (PET) scan.

Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. Read More

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http://dx.doi.org/10.1007/s00259-020-04831-wDOI Listing

Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest -Secretase Enzymatic Activity Involved in Alzheimer's Disease.

Biomed Res Int 2020 11;2020:8934289. Epub 2020 May 11.

Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, 22060, Pakistan.

Proteases BACE1 (-secretases) enzymes have been recognized as a promising target associated with Alzheimer's disease (AD). This study was carried out on the principles of molecular docking, chemical synthesis, and enzymatic inhibition of BACE1 enzymes via biaryl guanidine-based ligands. Based on virtual screening, thirteen different compounds were synthesized and subsequently evaluated via and studies. Read More

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http://dx.doi.org/10.1155/2020/8934289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238388PMC

Sporadic Creutzfeldt-Jakob Disease: Case Report and Literature Review.

Cureus 2020 Apr 21;12(4):e7767. Epub 2020 Apr 21.

Neurology, Marcus Neuroscience Institute, Boca Raton Regional Hospital, Boca Raton, USA.

The proverbial "zebras" in neurology are often times missed due to their low prevalence and incidence in the community. The number of misdiagnoses and improper therapeutic interventions that occur are further increased when patients with these rare diseases present with signs and symptoms of more common disorders. One such disease is sporadic Creutzfeldt-Jakob disease (sCJD), a prion disease that causes neuronal derangement and classically presents as a rapidly progressing dementia with extrapyramidal signs, ataxia, behavioural problems, and myoclonus in the advanced stage. Read More

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http://dx.doi.org/10.7759/cureus.7767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243655PMC

Systematic metabolic analysis of potential target, therapeutic drug, diagnostic method and animal model applicability in three neurodegenerative diseases.

Aging (Albany NY) 2020 May 27;12. Epub 2020 May 27.

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, Yunnan, China.

Considerable evidence suggests that metabolic abnormalities are associated with neurodegenerative diseases. This study aimed to conduct a systematic metabolic analysis of Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Human and mouse model microarray datasets were downloaded from the Gene Expression Omnibus database. Read More

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http://dx.doi.org/10.18632/aging.103253DOI Listing

Nutrition and the ageing brain: Moving towards clinical applications.

Ageing Res Rev 2020 May 24:101079. Epub 2020 May 24.

Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address:

The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3 Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. Read More

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http://dx.doi.org/10.1016/j.arr.2020.101079DOI Listing

Stress and Alzheimer's Disease: A Senescence Link?

Neurosci Biobehav Rev 2020 May 24. Epub 2020 May 24.

Department of Integrative Biology and Physiology and 2 Graduate Program in Neuroscience, University of Minnesota, United States. Electronic address:

Chronic stress has been shown to promote numerous aging-related diseases, and to accelerate the aging process itself. Of particular interest is the impact of stress on Alzheimer's Disease (AD), the most prevalent form of dementia. The vast majority of AD cases have no known genetic cause, making it vital to identify the environmental factors involved in the onset and progression of the disease. Read More

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http://dx.doi.org/10.1016/j.neubiorev.2020.05.010DOI Listing

Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate.

Am J Geriatr Psychiatry 2020 May 5. Epub 2020 May 5.

Johns Hopkins University School of Medicine (NJ, PBR), Baltimore, MD.

The public health burden of Alzheimer's disease (AD) is related not only to cognitive symptoms, but also to neuropsychiatric symptoms, including apathy. Apathy is defined as a quantitative reduction of goal-directed activity in comparison to a previous level of functioning and affects 30%-70% of persons with AD. Previous attempts to treat apathy in AD-both nonpharmacologically and pharmacologically-have been wanting. Read More

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http://dx.doi.org/10.1016/j.jagp.2020.04.026DOI Listing

The compensatory phenomenon of the functional connectome related to pathological biomarkers in individuals with subjective cognitive decline.

Transl Neurodegener 2020 May 27;9(1):21. Epub 2020 May 27.

Department of Neurology, Drum Tower Hospital, Medical School and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, P. R. China.

Background: Subjective cognitive decline (SCD) is a preclinical stage along the Alzheimer's disease (AD) continuum. However, little is known about the aberrant patterns of connectivity and topological alterations of the brain functional connectome and their diagnostic value in SCD.

Methods: Resting-state functional magnetic resonance imaging and graph theory analyses were used to investigate the alterations of the functional connectome in 66 SCD individuals and 64 healthy controls (HC). Read More

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http://dx.doi.org/10.1186/s40035-020-00201-6DOI Listing

Transplantation of bone marrow mesenchymal stem cells improves cognitive deficits and alleviates neuropathology in animal models of Alzheimer's disease: a meta-analytic review on potential mechanisms.

Transl Neurodegener 2020 May 27;9(1):20. Epub 2020 May 27.

Department of International Medical Service & Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1, Dong Cheng District, Beijing, 100730, China.

Background: Alzheimer's disease is a neurodegenerative disorder. Therapeutically, a transplantation of bone marrow mesenchymal stem cells (BMMSCs) can play a beneficial role in animal models of Alzheimer's disease. However, the relevant mechanism remains to be fully elucidated. Read More

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http://dx.doi.org/10.1186/s40035-020-00199-xDOI Listing

The Alzheimer's Prevention Initiative Composite Cognitive Test: a practical measure for tracking cognitive decline in preclinical Alzheimer's disease.

Alzheimers Res Ther 2020 May 27;12(1):66. Epub 2020 May 27.

Pentara Corporation, 2261 E. 3300 S. Suite 200, Salt Lake City, UT, USA.

Background: There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer's disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial. Read More

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http://dx.doi.org/10.1186/s13195-020-00633-2DOI Listing

APOE ε4 genotype-dependent cerebrospinal fluid proteomic signatures in Alzheimer's disease.

Alzheimers Res Ther 2020 May 27;12(1):65. Epub 2020 May 27.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.

Background: Aggregation of amyloid β into plaques in the brain is one of the earliest pathological events in Alzheimer's disease (AD). The exact pathophysiology leading to dementia is still uncertain, but the apolipoprotein E (APOE) ε4 genotype plays a major role. We aimed to identify the molecular pathways associated with amyloid β aggregation using cerebrospinal fluid (CSF) proteomics and to study the potential modifying effects of APOE ε4 genotype. Read More

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http://dx.doi.org/10.1186/s13195-020-00628-zDOI Listing

The association between genetic variants in lactotransferrin and dental caries: a meta- and gene-based analysis.

BMC Med Genet 2020 May 27;21(1):114. Epub 2020 May 27.

Division of Statistics, School of Economics, Shanghai University, 99 Shangda Rd, Baoshan Dist, Shanghai, 200444, China.

Background: The pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in lactotransferrin (LTF) and the risk of dental caries with inconsistent results.

Methods: A systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases was performed by two authors independently for papers published before December 5, 2019 on the association between genetic variants in LTF and the risk of dental caries. Read More

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http://dx.doi.org/10.1186/s12881-020-01029-7DOI Listing

Advanced glycation end products and protein carbonyl levels in plasma reveal sex-specific differences in Parkinson's and Alzheimer's disease.

Redox Biol 2020 May 18;34:101546. Epub 2020 May 18.

Department of Neurology, University Clinic Bonn, Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Electronic address:

Neurodegenerative diseases (NDD) such as Alzheimer's (AD) and Parkinson's disease (PD) are distinct clinical entities, however, the aggregation of key neuronal proteins, presumably leading to neuronal demise appears to represent a common mechanism. It has become evident, that advanced glycation end products (AGEs) trigger the accumulation of such modified proteins, which eventually contributes to pathological aspect of NDDs. Increased levels of AGEs are found in amyloid plaques in AD brains and in both advanced and early PD (incidental Lewy body disease). Read More

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http://dx.doi.org/10.1016/j.redox.2020.101546DOI Listing

Matrix Metalloproteinases as New Targets in Alzheimer's Disease: Opportunities and Challenges.

J Med Chem 2020 May 27. Epub 2020 May 27.

Although matrix metalloproteinases (MMPs) are implicated in the regulation of numerous physiological processes, evidence of their pathological roles have also been obtained in the last decades, making MMPs attractive therapeutic targets for several diseases. Recent discoveries of their involvement in central nervous system (CNS) disorders, and in particular in Alzheimer's disease (AD), have paved the way to consider MMP modulators as promising therapeutic strategies. Over the past few decades, diverse approaches have been undertaken in the design of therapeutic agents targeting MMPs for various purposes, leading, more recently, to encouraging developments. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.0c00352DOI Listing

Effects of Disulfide Bonds on Bindings of Inhibitors to BACE1 Decoded by Multiple Replica Accelerated Molecular Dynamics Simulations.

ACS Chem Neurosci 2020 May 27. Epub 2020 May 27.

The β-amyloid cleaving enzyme 1 (BACE1) has been thought as an efficient target for treatment of Alzheimer's disease (AD). Deep insight into inhibitor-BACE1 binding mechanism is of significance for design of potent drugs toward BACE1. In this work, multiple replica accelerated molecular dynamics (MR-aMD) simulations, principal component (PC) analysis and free energy landscapes were integrated to decode effect of disulfide bonds (SSBs) in BACE1 on bindings of three inhibitors 3KO, 3KT and 779 to BACE1. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00234DOI Listing

The role of the gut microbiota in the pathophysiology of mental and neurological disorders.

Psychiatr Genet 2020 May 26. Epub 2020 May 26.

Eurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, Reus, Spain.

In recent decades, the concept of the gut microbiota as a potential novel therapeutic strategy for mental health has emerged. The tiny microbes inhabiting our gut communicate through a bidirectional communication signaling with the brain that influences gut physiology, brain function and behavior. Accumulating evidence suggests that perturbation of the gut microbiota contributes to the pathophysiology of mental illnesses including autism, depression and anxiety as well as neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Read More

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http://dx.doi.org/10.1097/YPG.0000000000000255DOI Listing

Mobile Personal Healthcare System for Non-Invasive, Pervasive and Continuous Blood Pressure Monitoring: A Feasibility Study.

JMIR Mhealth Uhealth 2020 Apr 26. Epub 2020 Apr 26.

Departments of Neurosciences and Human Genetics, and Rio Grande Valley Alzheimer´s Disease Resource Center for Minority Aging Research, University of Texas Rio Grande Valley, Brownsville, US.

Background: Smartphone-based blood pressure (BP) monitor using photoplethysmogram (PPG) technology has emerged as a promising approach to empower users with self-monitoring for effective diagnosis and control of hypertension (HT).

Objective: This study aimed to develop a mobile personal healthcare system for non-invasive, pervasive, and continuous estimation of BP level and variability to be user-friendly to elderly.

Methods: The proposed approach was integrated by a self-designed cuffless, calibration-free, wireless and wearable PPG-only sensor, and a native purposely-designed smartphone application using multilayer perceptron machine learning techniques from raw signals. Read More

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http://dx.doi.org/10.2196/18012DOI Listing

The dichotomous role of the gut microbiome in exacerbating and ameliorating neurodegenerative disorders.

Expert Rev Neurother 2020 May 27. Epub 2020 May 27.

Department of Neurology, Mount Sinai School of Medicine , New York, NY 10029, USA.

Introduction: Age related neurodegenerative disorders affect millions of people around the world. The role of the gut microbiome (GM) in neurodegenerative disorders has been elucidated over the past few years. Dysbiosis of the gut microbiome ultimately results in neurodegeneration. Read More

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http://dx.doi.org/10.1080/14737175.2020.1775585DOI Listing

An Ecologically Valid, Longitudinal, and Unbiased Assessment of Treatment Efficacy in Alzheimer Disease (the EVALUATE-AD Trial): Proof-of-Concept Study.

JMIR Res Protoc 2020 May 27;9(5):e17603. Epub 2020 May 27.

Department of Neurology, Oregon Health and Science University, Portland, OR, United States.

Background: The current clinical trial assessment methodology relies on a combination of self-report measures, cognitive and physical function tests, and biomarkers. This methodology is limited by recall bias and recency effects in self-reporting and by assessments that are brief, episodic, and clinic based. Continuous monitoring of ecologically valid measures of cognition and daily functioning in the community may provide a more sensitive method to detect subtle, progressive changes in patients with cognitive impairment and dementia. Read More

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http://dx.doi.org/10.2196/17603DOI Listing

Regulation of aberrant proteasome activity re-establishes plasticity and long-term memory in an animal model of Alzheimer's disease.

FASEB J 2020 May 27. Epub 2020 May 27.

Department of Physiology, National University of Singapore, Singapore, Singapore.

Reduced retrograde memory performance at the cognitive level and aggregation/deposition of amyloid beta (Aβ) in the brain at the cellular level are some of the hallmarks of Alzheimer's Disease (AD). A molecular system that participates in the removal of proteins with an altered conformation is the Ubiquitin-Proteasome System (UPS). Impairments of the UPS in wild-type (WT) mice lead to defective clearance of Aβ and prevent long-term plasticity of synaptic transmission. Read More

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http://dx.doi.org/10.1096/fj.201902844RRDOI Listing

Driving force to detect Alzheimer's disease biomarkers: application of a thioflavine T@Er-MOF ratiometric fluorescent sensor for smart detection of presenilin 1, amyloid β-protein and acetylcholine.

Analyst 2020 May 27. Epub 2020 May 27.

Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry (Tianjin Normal University), Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecule, College of Chemistry, Tianjin Normal University, 393 Binshui West Road, Tianjin 300387, PR China. and Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Chemistry, Nankai University, Tianjin 300071, PR China.

Currently, the highly sensitive detection of Alzheimer's Disease (AD) biomarkers, namely presenilin 1, amyloid β-protein (Aβ), and acetylcholine (ACh), is vital to helping us prevent and diagnose AD. In this work, a novel metal-organic framework [Er(L)(DMF)1.27]n (Er-MOF) (H3L = terphenyl-3,4'',5-tricarboxylic acid) has been synthesized by solvothermal and ultrasonic methods. Read More

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http://dx.doi.org/10.1039/d0an00440eDOI Listing

High-altitude Tibetan fermented milk ameliorated cognitive dysfunction by modified gut microbiota in Alzheimer's disease transgenic mice.

Food Funct 2020 May 27. Epub 2020 May 27.

Research Center for High Altitude Medicine, Qinghai University, Key Laboratory for Application of High Altitude Medicine in Qinghai Province, Xining, China. and Qinghai University Affiliated Hospital, Xining, China.

Alzheimer's disease (AD) is a complex neurodegenerative disease that is regarded as a growing global challenge. Accumulating evidence linking gut microbiota with AD has become intriguing. The purpose of this study was to investigate how Tibetan fermented milk affected memory impairment in amyloid precursor protein (APP)/presenilin-1 (PS1) mice, using APP/PS1 transgenic mice as examples. Read More

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http://dx.doi.org/10.1039/c9fo03007gDOI Listing