176,825 results match your criteria Alzheimer's Disease and APOE-4


Chromolaena odorata (Siam weed): A natural reservoir of bioactive compounds with potent anti-fibrillogenic, antioxidative, and cytocompatible properties.

Biomed Pharmacother 2021 Jun 18;141:111811. Epub 2021 Jun 18.

Department of Chemistry, Faculty of Physical Sciences, Alex-Ekwueme Federal University, Ndufu-Alike Ikwo, Ebonyi State, Nigeria. Electronic address:

Protein fibrillation and oxidative damage are closely associated with the development of many chronic diseases such as Alzheimer's disease, Parkinson's disease and transthyretin amyloidoses. This work aimed at evaluating the fibrillogenic, antioxidant, anti-oxidative, hemolytic and cytotoxic activities of phenolic-rich extract from Chromolaena odorata (L) R.M. Read More

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Natural spirocyclic alkaloids and polyphenols as multi target dementia leads.

Bioorg Med Chem 2021 Jun 10;43:116270. Epub 2021 Jun 10.

Applied Chemistry & Environmental Science, School of Science, RMIT University, GPO Box 2476, Melbourne, VIC 3001, Australia.

The U rhynchophylla, U tomentosa, Isatis indigotica Fortune, Voacanga Africana, herbal constituents, fungal extracts from Aspergillus duricaulis culture media, include spirooxindoles, polyphenols or bridged spirocyclic alkaloids. Their constituents exhibit specific and synergistic multiple neuroprotective properties including inhibiting of Aβ fibril induced cytotoxicity, NMDA receptor inhibition in mice models of Alzheimer's disease (AD). The pioneering research from Woodward to Waldmann has advanced the synthesis of spirocyclic alkaloids. Read More

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Amyloid-PET imaging offers small improvements in predictions of future cognitive trajectories.

Neuroimage Clin 2021 Jun 8;31:102713. Epub 2021 Jun 8.

Department of Epidemiology and Biostatistics, University of California San Francisco, United States. Electronic address:

Background: Amyloid β (Aβ) is thought to initiate a cascade of pathology culminating in Alzheimer's disease-related cognitive decline. Aβ accumulation in brain tissues may begin one to two decades prior to clinical diagnosis of Alzheimer's disease. Prior studies have demonstrated that Aβ detected in vivo with positron emission tomography with amyloid ligands (amyloid-PET) predicts contemporaneously measured cognition and future cognitive trajectories. Read More

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Differential trajectories of hypometabolism across cognitively-defined Alzheimer's disease subgroups.

Neuroimage Clin 2021 Jun 12;31:102725. Epub 2021 Jun 12.

Department of Medicine, University of Washington, Seattle, WA, USA.

Disentangling biologically distinct subgroups of Alzheimer's disease (AD) may facilitate a deeper understanding of the neurobiology underlying clinical heterogeneity. We employed longitudinal [F]FDG-PET standardized uptake value ratios (SUVRs) to map hypometabolism across cognitively-defined AD subgroups. Participants were 384 amyloid-positive individuals with an AD dementia diagnosis from ADNI who had a total of 1028 FDG-scans (mean time between first and last scan: 1. Read More

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Temporal stability of the ventral attention network and general cognition along the Alzheimer's disease spectrum.

Neuroimage Clin 2021 Jun 14;31:102726. Epub 2021 Jun 14.

Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA; Indiana University Network Science Institute, Bloomington, IN, USA; Department of Radiology and Imaging Sciences, Indiana University School of Medicine (IUSM), Indianapolis, IN, USA; Indiana Alzheimer's Disease Research Center, IUSM, Indianapolis, IN, USA.

Understanding the interrelationships of clinical manifestations of Alzheimer's disease (AD) and functional connectivity (FC) as the disease progresses is necessary for use of FC as a potential neuroimaging biomarker. Degradation of resting-state networks in AD has been observed when FC is estimated over the entire scan, however, the temporal dynamics of these networks are less studied. We implemented a novel approach to investigate the modular structure of static (sFC) and time-varying (tvFC) connectivity along the AD spectrum in a two-sample Discovery/Validation design (n = 80 and 81, respectively). Read More

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Modularity and granularity across the language network-A primary progressive aphasia perspective.

Cortex 2021 May 24;141:482-496. Epub 2021 May 24.

Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Northwestern University Feinberg School of Medicine, Department of Psychiatry and Behavioral Sciences, Chicago, IL, USA.

Tests of grammar, repetition and semantics were administered to 62 prospectively enrolled right-handed participants with primary progressive aphasia (PPA). Structural brain images were obtained at the time of testing. Regression analyses uncovered 3 clearly delineated non-overlapping left hemisphere clusters where cortical thinning (atrophy) was significantly correlated with impaired performance. Read More

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Recent advances of quinones as a privileged structure in drug discovery.

Eur J Med Chem 2021 Jun 15;223:113632. Epub 2021 Jun 15.

Department of Clinical Pharmacy, Qilu Hospital of Shandong University, 250012, Jinan, PR China. Electronic address:

Privileged structures are conductive to discover novel bioactive substances because they can bind to multiple targets with high affinity. Quinones are considered to be a privileged structure and useful template for the design of new compounds with potential pharmacological activity. This article presents the recent developments (2014-2021 update) of quinones in the fields of antitumor, antibacterial, antifungal, antiviral, anti-Alzheimer's disease (AD) and antimalarial, mainly focusing on biological activities, structural modification and mechanism of action. Read More

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Cross-Sectional and Longitudinal Associations Between Adherence to Mediterranean Diet with Physical Performance and Cognitive Function in Older Adults: A Systematic Review And Meta-Analysis.

Ageing Res Rev 2021 Jun 18:101395. Epub 2021 Jun 18.

National Institute of Gastroenterology "Saverio de Bellis", Research Hospital, Castellana Grotte, Bari, Italy. Electronic address:

Objectives: The present study investigated the association between adherence to Mediterranean diet (MeDi) and physical performance and cognitive function in older adults.

Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated older adults aged 60+ years and assessed adherence to MeDi diet using validated composite scores. Observational studies, including cross-sectional, case-control, and longitudinal cohort studies, if crude baseline data was available, which investigated as a primary or secondary outcome the association of MeDi diet adherence with physical performance and/or cognitive function in non-demented older adults were included in the cross-sectional analysis. Read More

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Design, synthesis and biological evaluation of novel deoxyvasicinone-indole as multi-target agents for Alzheimer's disease.

Bioorg Med Chem Lett 2021 Jun 18:128212. Epub 2021 Jun 18.

Department of Chemistry, Kakatiya University, Warangal, Telangana, India. Electronic address:

In this study, a series of multifunctional hybrids (6a-6l) against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of deoxyvasicinone and indole. These analogs of deoxyvasicinone-indole were evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and as inhibitors of amyloid aggregation (Aβ) for treatment of Alzheimer's disease (AD). Subsequently, AChE induced Aβ aggregation inhibition test was also performed for selected compounds. Read More

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The association of epigenetic clocks in brain tissue with brain pathologies and common aging phenotypes.

Neurobiol Dis 2021 Jun 18:105428. Epub 2021 Jun 18.

Rush Alzheimer's Disease Center, Chicago, IL, United States of America; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States of America.

Epigenetic clocks are calculated by combining DNA methylation states across select CpG sites to estimate biologic age, and have been noted as the most successful markers of biologic aging to date. Yet, limited research has considered epigenetic clocks calculated in brain tissue. We used DNA methylation states in dorsolateral prefrontal cortex specimens from 721 older participants of the Religious Orders Study and Rush Memory and Aging Project, to calculate DNA methylation age using four established epigenetic clocks: Hannum, Horvath, PhenoAge, GrimAge, and a new Cortical clock. Read More

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Ceftriaxone regulates glutamate production and vesicular assembly in presynaptic terminals through GLT-1 in APP/PS1 mice.

Neurobiol Learn Mem 2021 Jun 18:107480. Epub 2021 Jun 18.

Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, P. R. China. Electronic address:

Perturbations in the glutamate-glutamine cycle and glutamate release from presynaptic terminals have been involved in the development of cognitive deficits in Alzheimer's disease (AD) patients and mouse models. Glutamate transporter-1 (GLT-1) removes glutamate from the synaptic cleft and transports it into astrocytes, where it is used as substrate for the glutamate-glutamine cycle. Ceftriaxone has been reported to improve cognitive deficits in AD mice by increasing GLT-1 expression, glutamate transformation to glutamine, and glutamine efflux from astrocytes. Read More

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Longitudinal stability of resting-state networks in normal aging, mild cognitive impairment, and Alzheimer's disease.

Magn Reson Imaging 2021 Jun 18. Epub 2021 Jun 18.

Department of Radiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Test-retest reliability is essential for using resting-state functional magnetic resonance imaging (rs-fMRI) as a potential biomarker for Alzheimer's disease (AD), especially when monitoring longitudinal changes and treatment effects. In addition, test-retest variability itself might represent a feature of AD. Using 3. Read More

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Molecular insight into the early stage of amyloid-β(1-42) Homodimers aggregation influenced by histidine tautomerism.

Int J Biol Macromol 2021 Jun 18. Epub 2021 Jun 18.

Department of Chemistry, Sungkyunkwan University, Suwon 16419, South Korea. Electronic address:

Aggregated amyloid β-peptide (Aβ) in small oligomeric forms inside the brain causes synaptic function disruption and the development of Alzheimer's disease (AD). Histidine is an important amino acid that may lead to structural changes. Aβ42 monomer chain includes 3 histidine residues that considering two ε and δ tautomers 8 isomers, including (εεε) and (εδδ) could be formed. Read More

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ER stress associated TXNIP-NLRP3 inflammasome activation in hippocampus of human Alzheimer's disease.

Neurochem Int 2021 Jun 18:105104. Epub 2021 Jun 18.

Department of Anatomy and Neurobiology; Neuroscience Institute, University of Tennessee Health Science Center, Memphis TN, 38163, USA. Electronic address:

Although the exact etiology of Alzheimer's disease (AD) is poorly understood, experimental and clinical evidences suggest the contribution of neuroinflammation in the pathogenesis of AD. Pathologically, AD brain is characterized by imbalance in redox status, elevated endoplasmic reticulum (ER) stress, synaptic dysfunction, inflammation and progressive neurodegeneration. It has been noted that continuous accumulation of amyloid-beta (Aβ) and intracellular neurofibrillary tangles (NFTs) in AD brain trigger ER stress, which contributes to neurodegeneration. Read More

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MicroRNA-23b attenuates tau pathology and inhibits oxidative stress by targeting GnT-III in Alzheimer's disease.

Neuropharmacology 2021 Jun 18:108671. Epub 2021 Jun 18.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:

Alzheimer's disease (AD) is a neurodegenerative disease, the main pathological features include deposition of neurofibrillary tangles composed of the abnormally hyperphosphorylated tau protein and plaques deposition composed of β-amyloid (Aβ) peptide. MicroRNAs and aberrant glycosylation both play key roles in a variety of diseases especially AD. Our previous study showed that N-acetylglucosaminyltransferase III (GnT-III) was expressed strongly in AD model mice. Read More

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The burden of neurological comorbidities in six autoimmune bullous diseases: A population-based study.

J Eur Acad Dermatol Venereol 2021 Jun 21. Epub 2021 Jun 21.

Lűbeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.

Background: Apart from bullous pemphigoid (BP), the association of other autoimmune bullous diseases (AIBDs) with neurological conditions is poorly understood.

Objective: To estimate the association between a wide array of AIBDs and neurological conditions.

Methods: A retrospective cross-sectional study recruited patients with BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV), and pemphigus foliaceus (PF). Read More

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The blood-brain and gut-vascular barriers: from the perspective of claudins.

Tissue Barriers 2021 Jun 21:1926190. Epub 2021 Jun 21.

FIRC Institute of Molecular Oncology, Milan, Italy.

In some organs, such as the brain, endothelial cells form a robust and highly selective blood-to-tissue barrier. However, in other organs, such as the intestine, endothelial cells provide less stringent permeability, to allow rapid exchange of solutes and nutrients where needed. To maintain the structural and functional integrity of the highly dynamic blood-brain and gut-vascular barriers, endothelial cells form highly specialized cell-cell junctions, known as adherens junctions and tight junctions. Read More

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Selective Pseudo-irreversible Butyrylcholinesterase Inhibitors Transferring Antioxidant Moieties to the Enzyme Show Pronounced Neuroprotective Efficacy In Vitro and In Vivo in an Alzheimer's Disease Mouse Model.

J Med Chem 2021 Jun 21. Epub 2021 Jun 21.

Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Julius Maximilian University of Würzburg, Am Hubland, 97074 Würzburg, Germany.

A series of multitarget-directed ligands (MTDLs) was designed by functionalizing a pseudo-irreversible butyrylcholinesterase (BChE) inhibitor. The obtained hybrids were investigated in vitro regarding their BChE and AChE inhibition, their enzyme kinetics, and their antioxidant physicochemical properties (DPPH, ORAC, metal chelating). In addition, in vitro assays were applied to investigate antioxidant effects using murine hippocampal HT22 cells and immunomodulatory effects on the murine microglial N9 cell line. Read More

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Cryptic Sites in Tau Fibrils Explain the Preferential Binding of the AV-1451 PET Tracer toward Alzheimer's Tauopathy.

ACS Chem Neurosci 2021 Jun 21. Epub 2021 Jun 21.

Department of Physics and Astronomy, Uppsala University, Uppsala SE-75120, Sweden.

Tauopathies are a subclass of neurodegenerative diseases characterized by an accumulation of microtubule binding tau fibrils in brain regions. Diseases such as Alzheimer's (AD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and corticobasal degeneration (CBD) belong to this subclass. Development of tracers which can visualize and discriminate between different tauopathies is of clinical importance in the diagnosis of various tauopathies. Read More

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Chronic stress and Alzheimer's disease.

Biotechnol Appl Biochem 2021 Jun 21. Epub 2021 Jun 21.

Neuroscience and Addiction Studies Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Stress is a key factor in the development and progress of the diseases. In neurodegenerative conditions, stress management can play an important role in maintaining quality of life and the capacity to improve. Neurodegenerative diseases, including Alzheimer's disease, cause motor and cognitive malfunctions that are spontaneously stressful and also can disturb the neural circuits that promote stress responses. Read More

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Translation and psychometric evaluation of a Persian version of the functional assessment staging scale (I-FAST) in older patients with mild cognitive impairment and Alzheimer's disease in Iran.

Acta Neurol Belg 2021 Jun 21. Epub 2021 Jun 21.

Cognition and Memory Studies, Yaadmaan Institute for Brain, Tehran, Iran.

The Functional Assessment Staging procedure is a clinical instrument which has been designed for staging Alzheimer's disease (AD) from the stage of no deficits to the pre-clinical stage of subjective deficits, to Mild Cognitive Impairment (MCI), to the stages of AD. This study examined the psychometric properties and the validity of the Persian version of the FAST (I-FAST) in an elderly outpatient population in Iran. We conducted a validation study of the FAST scale at the two referral centers for dementia and cognitive disorders in Tehran, Iran. Read More

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Modeling structural interconversion in Alzheimers' amyloid beta peptide with classical and intrinsically disordered protein force fields.

J Biomol Struct Dyn 2021 Jun 21:1-18. Epub 2021 Jun 21.

Department of Chemistry, University of California, Riverside, CA, USA.

A comprehensive understanding of the aggregation mechanism in amyloid beta 42 (Aβ42) peptide is imperative for developing therapeutic drugs to prevent or treat Alzheimer's disease. Because of the high flexibility and lack of native tertiary structures of Aβ42, molecular dynamics (MD) simulations may help elucidate the peptide's dynamics with atomic details and collectively improve ensembles not seen in experiments. We applied microsecond-timescale MD simulations to investigate the dynamics and conformational changes of Aβ42 by using a newly developed Amber force field ( We compared the and the regular force field by examining the conformational changes of two distinct Aβ42 monomers in explicit solvent. Read More

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Association of mitochondrial variants and haplogroups identified by whole exome sequencing with Alzheimer's disease.

Alzheimers Dement 2021 Jun 20. Epub 2021 Jun 20.

Department of Medicine (Biomedical Genetics), Boston University School of Medicine, 72 East Concord Street, Boston, Massachusetts, 02118, USA.

Introduction: Findings regarding the association between mitochondrial DNA (mtDNA) variants and Alzheimer's disease (AD) are inconsistent.

Methods: We developed a pipeline for accurate assembly and variant calling in mitochondrial genomes embedded within whole exome sequences (WES) from 10,831 participants from the Alzheimer's Disease Sequencing Project (ADSP). Association of AD risk was evaluated with each mtDNA variant and variants located in 1158 nuclear genes related to mitochondrial function using the SCORE test. Read More

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Effect of Age on Clinical Trial Outcome in Participants with Probable Alzheimer's Disease.

J Alzheimers Dis 2021 Jun 16. Epub 2021 Jun 16.

Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Age may affect treatment outcome in trials of mild probable Alzheimer's disease (AD).

Objective: We examined age as a moderator of outcome in an exploratory study of deep brain stimulation targeting the fornix (DBS-f) region in participants with AD.

Methods: Forty-two participants were implanted with DBS electrodes and randomized to double-blind DBS-f stimulation ("on") or sham DBS-f ("off") for 12 months. Read More

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Safety of Memantine in Combination with Potentially Interactive Drugs in the Real World: A Pharmacovigilance Study Using the Japanese Adverse Drug Event Report (JADER) Database.

J Alzheimers Dis 2021 Jun 17. Epub 2021 Jun 17.

Department of Neurology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Background: Memantine, an NMDA receptor antagonist, is used for the treatment of Alzheimer's disease. There is a caution to refrain from administrating memantine in combination with some specific drugs such as amantadine or dextromethorphan due to potential interactions that might augment the adverse effects of memantine.

Objective: This notification has not been validated in real-world data, which we aim to address using a large self-reporting database from Japan. Read More

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Decreased Levels of Insulin-Like Growth Factor-1 Are Associated with Alzheimer's Disease: A Meta-Analysis.

J Alzheimers Dis 2021 Jun 17. Epub 2021 Jun 17.

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing P.R. China.

Background: Alterations in levels of peripheral insulin-like growth factor-1 (IGF-1) in Alzheimer's disease (AD) have been reported in several studies, and results are inconsistent.

Objective: We conducted a meta-analysis to investigate the relationship between peripheral and cerebrospinal fluid IGF-1 levels and AD or mild cognitive impairment (MCI).

Methods: A systematic search in PubMed, Medline, Web of Science, Embase, and Cochrane Library was conducted and 18 studies were included. Read More

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Neural Mechanism of Shentai Tea Polyphenols on Cognitive Improvements for Individuals with Subjective Cognitive Decline: A Functional Near-Infrared Spectroscopy Study.

J Alzheimers Dis 2021 Jun 12. Epub 2021 Jun 12.

Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

Background: A growing awareness about non-pharmacological intervention for cognitively impaired individuals may represent an alternative therapeutic approach that is actively accepted by patients with very early stage of Alzheimer's disease. Understanding the neural basis of non-pharmacological intervention is a crucial step toward wide use for patients with cognitive disorders.

Objective: To investigate the underlying neural mechanism of shentai tea polyphenols in subjects with subjective cognitive decline (SCD) using functional near-infrared spectroscopy (fNIRS). Read More

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Porphyromonas gingivalis (W83) Infection Induces Alzheimer's Disease-Like Pathophysiology in Obese and Diabetic Mice.

J Alzheimers Dis 2021 Jun 16. Epub 2021 Jun 16.

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

Background: Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health.

Objective: This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer's disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model.

Methods: The db/db mice were either orally infected with P. Read More

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Frequencies and Neuropsychological Characteristics of Errors in the Clock Drawing Test.

J Alzheimers Dis 2021 Jun 15. Epub 2021 Jun 15.

Background: Few studies have investigated associations between types of clock drawing test (CDT) errors and cognitive impairment.

Objective: To explore associations of qualitative errors in the CDT with comprehensive neurocognitive assessment scores and clinical diagnosis.

Methods: Outpatients at a memory clinic were enrolled. Read More

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Blockage of Fc Gamma Receptors Alleviates Neuronal and Microglial Toxicity Induced by Palmitic Acid.

J Alzheimers Dis 2021 Jun 17. Epub 2021 Jun 17.

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Background: Palmitic acid (PA) promotes brain pathologies including Alzheimer's disease (AD)-related proteins, neuroinflammation, and microglial activation. The activation of neurons and microglia via their Fc gamma receptors (FcγRs) results in producing inflammatory cytokines.

Objective: To investigate the expression of FcγRs, FcγR signaling proteins, AD-related proteins, proinflammatory cytokines, and cell viability of neurons and microglia in association with PA exposure as well as the effects of FcγR blockade on these parameters in response to PA. Read More

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