95,817 results match your criteria Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis[Journal]


Accumulation of amyloid beta in human glioblastomas.

Clin Exp Immunol 2020 Jul 12. Epub 2020 Jul 12.

Physiology department, Medical School, Universidad Central del Caribe, Ave Laurel, Santa Juanita, Bayamon, PR 00956, Puerto Rico.

Many cancer types are intrinsically associated with specific types of amyloidosis, in which amyloidis accumulated locally inside tumors or systemically. Usually, this condition relates to the hyper-production of specific amylogenic proteins. Recently, we found that the accumulation of amyloid beta (Aβ) peptide immunofluorescence is linked to glioma cells in mouse tumors. Read More

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http://dx.doi.org/10.1111/cei.13493DOI Listing

Kidney transplantation as a treatment of choice for AA amyloidosis due to periodic fever syndrome.

Clin Rheumatol 2020 Jul 11. Epub 2020 Jul 11.

Department of Surgery and Transplantation Center, University Hospital Martin and Jessenius Medical Faculty of Comenius University, Kollárova 2, 03601, Martin, Slovak Republic.

Renal AA amyloidosis is the most serious complication of periodic fever syndrome, which, inadequate suppression, due to persistent inflammation, leads to nephrotic syndrome and renal failure over several years. In most cases, periodic fever syndromes begin to manifest clinically in early childhood. Occurrence in adulthood is considered rare and is associated with a poorer clinical course. Read More

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http://dx.doi.org/10.1007/s10067-020-05283-1DOI Listing

Poncirin, an orally active flavonoid exerts antidiabetic complications and improves glucose uptake activating PI3K/Akt signaling pathway in insulin resistant C2C12 cells with anti-glycation capacities.

Bioorg Chem 2020 Jun 30;102:104061. Epub 2020 Jun 30.

Department of Korean Medicine, Graduate School, Kyung Hee University, 26, Kyunghee dae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address:

Poncirin, a natural flavanone glycoside present abundantly in many citrus fruits, contains an extensive range of biological activities. However, the antidiabetic mechanism of poncirin is unexplored yet. In this study, we examined the anti-diabetic prospective of poncirin by evaluating its ability to inhibit protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant AR (HRAR), rat lens aldose reductase (RLAR), and advanced glycation end-product (AGE) formation (IC = 7. Read More

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http://dx.doi.org/10.1016/j.bioorg.2020.104061DOI Listing

Time to Redefine Risk-Stratification and Response Criteria in Immunoglobulin Light Chain Amyloidosis?

Clin Lymphoma Myeloma Leuk 2020 Jun 7. Epub 2020 Jun 7.

Department of Haematology, Oxford University Hospitals, NHS Foundation Trust; NIHR BRC Blood Theme, Oxford, England, UK; Oxford Myeloma Centre for Translational Research.

Immunoglobulin light chain (AL) amyloidosis results from clonal plasma cell (PC)-derived immunoglobulin light chain-mediated end-organ dysfunction, the extent and severity of which predicts survival. Anti-PC therapies reduce clonal light chain burden, which usually results in improvement of organ function, and consequently overall survival. Response assessment is critical to gauge therapeutic efficacy, to report clinical trial outcomes, and to switch therapy in those without response. Read More

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http://dx.doi.org/10.1016/j.clml.2020.05.025DOI Listing

Suppression of BACE1 and amyloidogenic/RAGE axis by sitagliptin ameliorates PTZ kindling-induced cognitive deficits in rats.

Chem Biol Interact 2020 Jul 9:109144. Epub 2020 Jul 9.

Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

The debilitating nature of cognitive impairment in epilepsy and the potential of some traditional antiepileptics to further deteriorate cognitive function are areas of growing concern. Glucagon-like peptide-1 (GLP-1) deficiency has been linked to reduced seizure threshold as well as cognitive dysfunction. Here, we tested whether sitagliptin (SITA), by virtue of its neuroprotective properties, could alleviate both epilepsy and associated cognitive dysfunction in a rat model of kindling epilepsy. Read More

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http://dx.doi.org/10.1016/j.cbi.2020.109144DOI Listing

A natural BACE1 and GSK3β dual inhibitor Notopterol effectively ameliorates the cognitive deficits in APP/PS1 Alzheimer's mice by attenuating amyloid-β and tau pathology.

Clin Transl Med 2020 Jul 11. Epub 2020 Jul 11.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.

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http://dx.doi.org/10.1002/ctm2.50DOI Listing

Synaptic Loss in Primary Tauopathies Revealed by [ C]UCB-J Positron Emission Tomography.

Mov Disord 2020 Jul 11. Epub 2020 Jul 11.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Background: Synaptic loss is a prominent and early feature of many neurodegenerative diseases.

Objectives: We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson's syndrome) and amyloid-negative corticobasal syndrome (CBS).

Methods: Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [ C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment. Read More

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http://dx.doi.org/10.1002/mds.28188DOI Listing

Pathogenesis of Alzheimer's disease: Multiple interacting causes against which amyloid precursor protein protects.

Med Hypotheses 2020 Jun 25;143:110035. Epub 2020 Jun 25.

Garburn House, Westmorland General Hospital, Burton Road, Kendal, Cumbria LA9 7RG, UK.

Alzheimer's disease is the commonest form of senile dementia. It is characterised by neuronal cell death and amyloid deposition. Amyloid precursor protein (APP), which is highly conserved in evolution, is expressed in neurones in response to a wide range of damaging agents. Read More

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http://dx.doi.org/10.1016/j.mehy.2020.110035DOI Listing

Design, synthesis and biological evaluation of rasagiline-clorgyline hybrids as novel dual inhibitors of monoamine oxidase-B and amyloid-β aggregation against Alzheimer's disease.

Eur J Med Chem 2020 Jun 30;202:112475. Epub 2020 Jun 30.

Department of Pharmacy, Affiated Tumor Hospital of Guangxi Medical University, Nanning, PR China. Electronic address:

A series of rasagiline-clorgyline hybrids was designed, synthesized and investigated in vitro for their inhibition of monoamine oxidase and amyloid-β aggregation. Most of compounds were found to be selective and highly potent hMAO-B inhibitors showing IC values in the nanomolar, and exhibited a moderate inhibition of amyloid-β aggregation. 7-((5-(methyl(prop-2-yn-1-yl)amino) pentyl)oxy)chroman-4-one (6j) was the most interesting compound identified in this research, endowed with higher hMAO-B potency (IC = 4 nM) and selectivity (SI > 25000) compared to the reference selective inhibitor rasagiline (IC = 141 nM, SI > 355), and exhibited good inhibitory activity against Aβ aggregation (40. Read More

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http://dx.doi.org/10.1016/j.ejmech.2020.112475DOI Listing

Wild-type Transthyretin Amyloidosis Occurring in the Ligamentum Flavum of the Cervicothoracic Spine.

World Neurosurg 2020 Jul 8. Epub 2020 Jul 8.

Tufts Medical Center, Department of Neurosurgery, 800 Washington St, Boston, MA, 02111.

Background: Wild-type transthyretin amyloid (ATTRwt) has been noted to deposit in the ligamentum flavum of the spine. Prior studies have focused on ATTRwt in the lumbar region, but there is a lack of studies discussing its presentation in other levels of the spine. We report on the presentation of patients with confirmed amyloid in the cervicothoracic regions, and discuss the literature to date. Read More

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http://dx.doi.org/10.1016/j.wneu.2020.06.228DOI Listing

Dopamine Improves Resistance of Dendrites of Mauthner Neurons to Destruction Induced by Sensory Stimulation and Application of Β-Amyloid.

Bull Exp Biol Med 2020 Jul 10. Epub 2020 Jul 10.

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region, Russia.

Mauthner neurons in goldfish fry were studied by the methods of light and electron microscopy. The structure and volume of individual dendrites as well as the structure of axodendritic synapses were examined using virtual images of neurons formed from serial 3-μ sections. In short-time (5 h) experiments with application of dopamine, β-amyloid fragment (25-35), and long-term sensory stimulation affecting afferent inputs to Mauthner neurons, the dendrites were larger than the same dendrites under the same conditions without dopamine application. Read More

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http://dx.doi.org/10.1007/s10517-020-04865-yDOI Listing

Robust light-dark patterns and reduced amyloid load in an Alzheimer's disease transgenic mouse model.

Sci Rep 2020 Jul 10;10(1):11436. Epub 2020 Jul 10.

Lighting Research Center, Rensselaer Polytechnic Institute, Troy, NY, USA.

Circadian disruption resulting from exposure to irregular light-dark patterns and sleep deprivation has been associated with beta amyloid peptide (Aβ) aggregation, which is a major event in Alzheimer's disease (AD) pathology. We exposed 5XFAD mice and littermate controls to dim-light vs. bright-light photophases to investigate the effects of altering photophase strength on AD-associated differences in cortical Aβ42 levels, wheel-running activity, and circadian free-running period (tauDD). Read More

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http://dx.doi.org/10.1038/s41598-020-68199-5DOI Listing

The Emerging Role of Nutraceuticals and Phytochemicals in the Prevention and Treatment of Alzheimer's Disease.

J Alzheimers Dis 2020 Jul 7. Epub 2020 Jul 7.

Laboratory of Neurosciences and Functional Medicine, International Center for Biomedicine (ICC) and Faculty of Sciences, University of Chile, Santiago, Chile.

One of the major challenges of medical sciences has been finding a reliable compound for the pharmacological treatment of Alzheimer's disease (AD). As most of the drugs directed to a variety of targets have failed in finding a medical solution, natural products from Ayurvedic medicine or nutraceutical compounds emerge as a viable preventive therapeutics' pathway. Considering that AD is a multifactorial disease, nutraceutical compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs used for AD treatment. Read More

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http://dx.doi.org/10.3233/JAD-200443DOI Listing

Neurodegeneration of Trigeminal Mesencephalic Neurons by the Tooth Loss Triggers the Progression of Alzheimer's Disease in 3×Tg-AD Model Mice.

J Alzheimers Dis 2020 Jul 9. Epub 2020 Jul 9.

Laboratory of Neurodegenerative Diseases, chool of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR.

Background: The mesencephalic trigeminal nucleus (Vmes) is not only anatomically adjacent to the locus coeruleus (LC) but is also tightly associated with the function of the LC. The LC can be the first area in which Alzheimer's disease (AD) develops, although it is unclear how LC neuronal loss occurs.

Objective: We investigated whether neuronal death in the Vmes can be spread to adjacent LC in female triple transgenic (3×Tg)-AD mice, how amyloid-β (Aβ) is involved in LC neuronal loss, and how this neurodegeneration affects cognitive function. Read More

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http://dx.doi.org/10.3233/JAD-200257DOI Listing

Whole-Exome Sequencing Analysis of Alzheimer's Disease in Non-APOE*4 Carriers.

J Alzheimers Dis 2020 Jul 8. Epub 2020 Jul 8.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

The genetics of late-onset Alzheimer's disease (AD) is complex due to the heterogeneous nature of the disorder. APOE*4 is the strongest genetic risk factor for AD. Genome-wide association studies have identified more than 30 additional loci, each having relatively small effect size. Read More

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http://dx.doi.org/10.3233/JAD-200037DOI Listing

Cerebrospinal Fluid Amyloid Beta, Tau Levels, Apolipoprotein, and H-MRS Brain Metabolites in Alzheimer's Disease: A Systematic Review.

Acad Radiol 2020 Jul 7. Epub 2020 Jul 7.

Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia, Selangor 43400, Malaysia.

Background: There is compelling evidence that neurochemical changes measured by proton magnetic resonance spectroscopy (H-MRS) occur at different phases of Alzheimer's disease (AD). However, the extent to which these neurochemical changes are associated with validated AD biomarkers and/or apolipoprotein (APOE) ε4 is yet to be established.

Objective: This systematic review analyzed the available evidence on (1) neurochemical changes; and (2) the relations between brain metabolite and validated cerebrospinal fluid biomarkers, and/or APOE in AD. Read More

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

Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma.

Cancers (Basel) 2020 Jul 8;12(7). Epub 2020 Jul 8.

Graduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, Taiwan.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, affecting over 700,000 people per year. The treatment effect in advanced HCC is still disappointing and prognosis of advanced HCC remains poor. Hence, to find more effective therapeutic targets to improve the treatment outcome of HCC is of urgent need. Read More

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http://dx.doi.org/10.3390/cancers12071843DOI Listing

Linking cognition to age and amyloid-β burden in the brain of a nonhuman primate (Microcebus murinus).

Neurobiol Aging 2020 Jun 14;94:207-216. Epub 2020 Jun 14.

MMDN, University of Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier, France.

The gray mouse lemur (Microcebus murinus) is a valuable model in research on age-related proteopathies. This nonhuman primate, comparable to humans, naturally develops tau and amyloid-β proteopathies during aging. Whether these are linked to cognitive alterations is unknown. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2020.03.025DOI Listing

Inhibitory Potency of 4- Substituted Sampangine Derivatives toward Cu mediated aggregation of amyloid β-peptide, Oxidative Stress, and Inflammation in Alzheimer's Disease.

Neurochem Int 2020 Jul 7:104794. Epub 2020 Jul 7.

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin City, Guangxi, China. Electronic address:

Cu plays a key role in the pathogenesis of Alzheimer's disease (AD). The dysregulation of Cu can cause neuronal damage and aggravate development of AD. Moreover, a series of 4-substituted sampangine derivatives have been investigated as inhibitors of acetylcholinesterase and β-amyloid (Aβ) aggregation for the treatment of AD in our previous studies. Read More

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http://dx.doi.org/10.1016/j.neuint.2020.104794DOI Listing

Predicted aggregation-prone region (APR) in βB1-crystallin forms the amyloid-like structure and induces aggregation of soluble proteins isolated from human cataractous eye lens.

Int J Biol Macromol 2020 Jul 7. Epub 2020 Jul 7.

Department of Biotechnology, Central University of Rajasthan, NH-8 Bandersindri, Kishangarh, Ajmer 305817, Rajasthan, India. Electronic address:

The aggregation of β-crystallins in the human eye lens constitutes a critical step during the development of cataract. We anticipated that the presence of Aggregation-prone Regions (APRs) in their primary structure, which might be responsible for conformational change required for the self-assembly. To examine the presence of APRs, we systematically analyzed the primary structures of β-crystallins. Read More

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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.028DOI Listing

Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor.

FASEB J 2020 Jul 10. Epub 2020 Jul 10.

Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain.

Human riboflavin kinase (HsRFK) catalyzes vitamin B (riboflavin) phosphorylation to flavin mononucleotide (FMN), obligatory step in flavin cofactor synthesis. HsRFK expression is related to protection from oxidative stress, amyloid-β toxicity, and some malignant cancers progression. Its downregulation alters expression profiles of clock-controlled metabolic-genes and destroys flavins protection on stroke treatments, while its activity reduction links to protein-energy malnutrition and thyroid hormones decrease. Read More

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http://dx.doi.org/10.1096/fj.202000566RDOI Listing

Varicella zoster virus encodes a viral decoy RHIM to inhibit cell death.

PLoS Pathog 2020 Jul 10;16(7):e1008473. Epub 2020 Jul 10.

Discipline of Infectious Diseases and Immunology, School of Medical Sciences, The University of Sydney, NSW, Australia.

Herpesviruses are known to encode a number of inhibitors of host cell death, including Rip Homotypic Interaction Motif (RHIM)-containing proteins. Varicella zoster virus (VZV) is a member of the alphaherpesvirus subfamily and is responsible for causing chickenpox and shingles. We have identified a novel viral RHIM in the VZV capsid triplex protein, open reading frame (ORF) 20, that acts as a host cell death inhibitor. Read More

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http://dx.doi.org/10.1371/journal.ppat.1008473DOI Listing

Small Molecule-Functionalized Hyperbranched Polyglycerol Dendrimer for Inhibiting Protein Aggregation.

Biomacromolecules 2020 Jul 10. Epub 2020 Jul 10.

Amyloid protein aggregation is responsible for variety of neurodegenerative diseases and anti-amyloidogenic small molecules are identified for inhibiting such protein aggregation at extra/intracellular space. We show that nanoparticle form of small molecules offer better anti-amyloidogenic performance via enhanced bioavailability and multivalent binding with protein. Here we report hyperbranched polyglycerol dendrimer terminated with anti-amyloidogenic small molecules such as gallate, tyrosine and trehalose and their potential in inhibiting lysozyme/huntingtin protein aggregation under intra/extracellular space. Read More

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http://dx.doi.org/10.1021/acs.biomac.0c00713DOI Listing

Alzheimer's Disease risk modifier genes do not affect tau aggregate uptake, seeding or maintenance in cell models.

FEBS Open Bio 2020 Jul 10. Epub 2020 Jul 10.

Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Alzheimer's disease (AD) afflicts millions of people worldwide and is caused by accumulated amyloid beta and tau pathology. Progression of tau pathology in AD may utilize prion mechanisms of propagation in which pathological tau aggregates released from one cell are taken up by neighboring or connected cells and act as templates for their own replication, a process termed "seeding." We have used HEK293T cells to model various aspects of pathological tau propagation, including uptake of tau aggregates, induced seeding by exogenous aggregates, seeding caused by Lipofectamine-mediated delivery to the cell interior, and stable maintenance of aggregates in dividing cells. Read More

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http://dx.doi.org/10.1002/2211-5463.12928DOI Listing

Green Fluorescent Protein Nanovessel Serves as a Nucleolus Targeting Material and Molecule Carrier in Living Cells.

Adv Biosyst 2019 Jul 3;3(7):e1900047. Epub 2019 Jun 3.

State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, College of Chemistry, and International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Jilin University, 2699 Qianjin Street, Changchun, 130012, P. R. China.

The nucleolus is responsible for RNA transcription, processing, and ribosome assembly, the dysfunction of which is associated with a number of diseases. In this report, a new member of fluorescent protein nanovessels (FPNs), constructed using thioflavin-T (ThT) and bovine serum albumin (BSA) as building blocks, is described. As a popular amyloid specific dye, ThT is nonfluorescent by itself, while its fluorescence can be lighted up upon interacting with amyloid proteins. Read More

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http://dx.doi.org/10.1002/adbi.201900047DOI Listing

Longitudinal validity of PET-based staging of regional amyloid deposition.

Hum Brain Mapp 2020 Jul 10. Epub 2020 Jul 10.

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.

Positron emission tomography (PET)-based staging of regional amyloid deposition has recently emerged as a promising tool for sensitive detection and stratification of pathology progression in Alzheimer's Disease (AD). Here we present an updated methodological framework for PET-based amyloid staging using region-specific amyloid-positivity thresholds and assess its longitudinal validity using serial PET acquisitions. We defined region-specific thresholds of amyloid-positivity based on Florbetapir-PET data of 13 young healthy individuals (age ≤ 45y), applied these thresholds to Florbetapir-PET data of 179 cognitively normal older individuals to estimate a regional amyloid staging model, and tested this model in a larger sample of patients with mild cognitive impairment (N = 403) and AD dementia (N = 85). Read More

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http://dx.doi.org/10.1002/hbm.25121DOI Listing

Diclofenac reduces the risk of Alzheimer's disease: a pilot analysis of NSAIDs in two US veteran populations.

Ther Adv Neurol Disord 2020 25;13:1756286420935676. Epub 2020 Jun 25.

School of Public Health and Information Sciences, University of Louisville, KY, USA.

Background: Our aim was to determine whether specific nonsteroidal anti-inflammatory (NSAID) agents are associated with a decreased frequency of Alzheimer's disease (AD).

Materials And Methods: Days of drug exposure were determined for diclofenac, etodolac, and naproxen using US Department of Veterans Affairs (VA) pharmacy transaction records, combined from two separate VA sites. AD diagnosis was established by the International Classification of Diseases, ninth revision (ICD-9)/ICD-10 diagnostic codes and the use of AD medications. Read More

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http://dx.doi.org/10.1177/1756286420935676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325551PMC

Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.

Mol Psychiatry 2020 Jul 10. Epub 2020 Jul 10.

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore.

A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Read More

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http://dx.doi.org/10.1038/s41380-020-0806-5DOI Listing

Clustering of human prion protein and α-synuclein oligomers requires the prion protein N-terminus.

Commun Biol 2020 Jul 9;3(1):365. Epub 2020 Jul 9.

Institute of Biological Information Processing (IBI-7) and JuStruct: Jülich Center for Structural Biology, Forschungszentrum Jülich, 52425, Jülich, Germany.

The interaction of prion protein (PrP) and α-synuclein (αSyn) oligomers causes synaptic impairment that might trigger Parkinson's disease and other synucleinopathies. Here, we report that αSyn oligomers (αSynO) cluster with human PrP (huPrP) into micron-sized condensates. Multivalency of αSyn within oligomers is required for condensation, since clustering with huPrP is not observed for monomeric αSyn. Read More

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http://dx.doi.org/10.1038/s42003-020-1085-zDOI Listing

F-SMBT-1: A Selective and Reversible Positron-Emission Tomography Tracer for Monoamine Oxidase-B Imaging.

J Nucl Med 2020 Jul 9. Epub 2020 Jul 9.

Tohoku Medical and Pharmaceutical University, Japan.

Reactive astrocytes play a key role in the pathogenesis of various neurodegenerative diseases. Monoamine oxidase-B (MAO-B) is one of the promising targets for the imaging of astrogliosis in the human brain. A novel selective and reversible MAO-B tracer, (S)-(2-methylpyrid-5-yl)-6-[(3-[F]fluoro-2-hydroxy)propoxy]quinoline, (F-SMBT-1), was successfully developed via lead optimization from first-generation tau positron-emission tomography (PET) tracer F-THK-5351. Read More

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http://dx.doi.org/10.2967/jnumed.120.244400DOI Listing

Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies.

Acta Neuropathol Commun 2020 Jul 9;8(1):103. Epub 2020 Jul 9.

Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, UK.

Neurons of the nucleus basalis of Meynert (nbM) are vulnerable to Lewy body formation and neuronal loss, which is thought to underlie cognitive dysfunction in Lewy body dementia (LBD). There is continued debate about whether Lewy bodies exert a neurodegenerative effect by affecting mitochondria, or whether they represent a protective mechanism. Therefore, the present study sought to determine whether the nbM is subject to mitochondrial dysfunctional in LBD and the association of Lewy body formation with such changes. Read More

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http://dx.doi.org/10.1186/s40478-020-00985-8DOI Listing

MicroRNAs Related to Cognitive Impairment After Hearing Loss.

Clin Exp Otorhinolaryngol 2020 Jul 11. Epub 2020 Jul 11.

Department of Otorhinolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.

Objectives: Our research group has previously demonstrated that hearing loss might be a risk factor for synaptic loss within the hippocampus and impairment of cognition using an animal model of Alzheimer disease. In this study, after inducing hearing loss in a rat model of Alzheimer disease, the associations of various microRNAs (miRNAs) with cognitive impairment were investigated.

Methods: Rats were divided randomly into two experimental groups: the control group, which underwent sham surgery and subthreshold amyloid-β infusion and the deaf group, which underwent bilateral cochlear ablation and subthreshold amyloid-β infusion. Read More

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http://dx.doi.org/10.21053/ceo.2019.01382DOI Listing

Steroids and Alzheimer's Disease: Changes Associated with Pathology and Therapeutic Potential.

Authors:
Yvette Akwa

Int J Mol Sci 2020 Jul 7;21(13). Epub 2020 Jul 7.

"Disease and Hormones of the Nervous System", U1195 Inserm-Université Paris Saclay, 80 rue du Général Leclerc, 94276 Kremlin-Bicêtre, France.

Alzheimer's disease (AD) is a multifactorial age-related neurodegenerative disease that today has no effective treatment to prevent or slow its progression. Neuroactive steroids, including neurosteroids and sex steroids, have attracted attention as potential suitable candidates to alleviate AD pathology. Accumulating evidence shows that they exhibit pleiotropic neuroprotective properties that are relevant for AD. Read More

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http://dx.doi.org/10.3390/ijms21134812DOI Listing

Neuroprotective effects of Fraxinus angustifolia Vahl. bark extract against Alzheimer's disease.

J Chem Neuroanat 2020 Jul 6:101848. Epub 2020 Jul 6.

Laboratoire de Biochimie Appliquée, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000, Bejaia, Algeria.

Alzheimer disease's (AD) is a neurodegenerative disease induced by amyloid-β aggregation and accumulation of neurotoxic metals in the brain. Fraxinus angustifolia Vahl. (Oleaceae) is a Mediterranean plant traditionally used to treat several human problems as nervous system problems. Read More

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http://dx.doi.org/10.1016/j.jchemneu.2020.101848DOI Listing

LRP1 knockdown aggravates Aβ-stimulated microglial and astrocytic neuroinflammatory responses by modulating TLR4/NF-κB/MAPKs signaling pathways.

Exp Cell Res 2020 Jul 6:112166. Epub 2020 Jul 6.

Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China. Electronic address:

Neuroinflammation is an important pathological feature and an early event in the pathogenesis of Alzheimer's disease (AD), which is characterized by activation of microglia and astrocytes. Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic receptor that is abundantly expressed in neurons, microglia, and astrocytes, and plays a critical role in AD pathogenesis. There is increasing evidence to show that LRP1 regulates inflammatory responses by modulating the release of pro-inflammatory cytokines and phagocytosis. Read More

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http://dx.doi.org/10.1016/j.yexcr.2020.112166DOI Listing

The phosphodiesterase-4 inhibitor roflumilast, a potential treatment for the comorbidity of memory loss and depression in Alzheimer's disease: a preclinical study in APP/PS1 transgenic mice.

Int J Neuropsychopharmacol 2020 Jul 9. Epub 2020 Jul 9.

Departments of Neuroscience and Behavioral Medicine & Psychiatry, the Rockefeller Neuroscience Institute, West Virginia University Health Sciences Center, Morgantown, WV, USA.

Background: Depression is highly related to Alzheimer's disease (AD),yet no effective treatment is available. Phosphodiesterase-4 (PDE4) has been considered a promising target for treatment of AD and depression. Roflumilast, the first PDE4 inhibitor approved for clinic use, improves cognition at doses that do not cause side effects such as emesis. Read More

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http://dx.doi.org/10.1093/ijnp/pyaa048DOI Listing

In vivo synthesis of bacterial amyloid curli contributes to joint inflammation during S. Typhimurium infection.

PLoS Pathog 2020 Jul 9;16(7):e1008591. Epub 2020 Jul 9.

Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America.

Reactive arthritis, an autoimmune disorder, occurs following gastrointestinal infection with invasive enteric pathogens, such as Salmonella enterica. Curli, an extracellular, bacterial amyloid with cross beta-sheet structure can trigger inflammatory responses by stimulating pattern recognition receptors. Here we show that S. Read More

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http://dx.doi.org/10.1371/journal.ppat.1008591DOI Listing

Correlation of pyroglutamate amyloid β and ptau Ser202/Thr205 levels in Alzheimer's disease and related murine models.

PLoS One 2020 9;15(7):e0235543. Epub 2020 Jul 9.

QPS Austria GmbH, Grambach, Austria.

Senile plaques frequently contain Aβ-pE(3), a N-terminally truncated Aβ species that is more closely linked to AD compared to other Aβ species. Tau protein is highly phosphorylated at several residues in AD, and specifically phosphorylation at Ser202/Thr205 is known to be increased in AD. Several studies suggest that formation of plaques and tau phosphorylation might be linked to each other. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235543PLOS

Fully bayesian longitudinal unsupervised learning for the assessment and visualization of AD heterogeneity and progression.

Aging (Albany NY) 2020 Jul 9;12. Epub 2020 Jul 9.

Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Tau pathology and brain atrophy are the closest correlate of cognitive decline in Alzheimer's disease (AD). Understanding heterogeneity and longitudinal progression of atrophy during the disease course will play a key role in understanding AD pathogenesis. We propose a framework for longitudinal clustering that simultaneously: 1) incorporates whole brain data, 2) leverages unequal visits per individual, 3) compares clusters with a control group, 4) allows for study confounding effects, 5) provides cluster visualization, 6) measures clustering uncertainty. Read More

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http://dx.doi.org/10.18632/aging.103623DOI Listing

A new dilignan from the twigs and leaves of .

J Asian Nat Prod Res 2020 Jul 9:1-6. Epub 2020 Jul 9.

Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

Previous work has shown that the lignans from the twigs and leaves of (Jack) I.C.N. Read More

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http://dx.doi.org/10.1080/10286020.2020.1791097DOI Listing

The Association Between Early Age-Related Hearing Loss and Brain β-Amyloid.

Laryngoscope 2020 Jul 9. Epub 2020 Jul 9.

Department of Medicine, Columbia University, New York, New York, U.S.A.

Objectives/hypothesis: To analyze the association between early audiometric age-related hearing loss and brain β-amyloid, the pathologic hallmark of Alzheimer's disease (AD).

Study Design: Cross-sectional analysis of a prospective cohort study.

Methods: A cross-sectional analysis was performed on 98 participants in a cohort study of hearing and brain biomarkers of AD. Read More

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http://dx.doi.org/10.1002/lary.28859DOI Listing

Up-regulation of neprilysin mediates the protection of fructo-oligosaccharides against Alzheimer's disease.

Food Funct 2020 Jul 9. Epub 2020 Jul 9.

Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, China.

Fructo-oligosaccharides (FOS), an important prebiotic, have been proved to have a beneficial effect on Alzheimer's disease (AD); however, the specific mechanism remains to be confirmed. Senile plaques are one of the main neuropathological features of AD and the core of senile plaques mainly consists of extracellular beta-amyloid (Aβ). Reducing Aβ accumulation in the brain is an important therapeutic strategy for AD. Read More

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http://dx.doi.org/10.1039/d0fo00161aDOI Listing

[Effect of electroacupuncture on recognition memory and levels of Aβ, inflammatory factor proteins and aquaporin 4 in hippocampus of APP/PS1 double transgenic mice].

Zhen Ci Yan Jiu 2020 Jun;45(6):431-7

School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Objective: To investigate the effect of electroacupuncture (EA) at "Baihui "(GV20) and "Shenshu "(BL23) on activation of glial cells, expression of inflammatory factor proteins and aquaporin 4 (AQP4)in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice, so as to explore its mechanisms underlying improvement of Alzheimer's disease(AD).

Methods: Twenty C57/BL6 background male APP695/PS1-dE9(APP/PS1) double transgenic mice (model group) and 20 wild type (WT) C57/BL6 mice (blank group) were respectively randomized into control and EA groups. EA (2 Hz/15 Hz, 1-2 mA) was applied to GV20 and bilateral BL23 for 30 min, once daily, 6 days a week for 4 weeks. Read More

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http://dx.doi.org/10.13702/j.1000-0607.190923DOI Listing

Nonlinear biomarker interactions in conversion from mild cognitive impairment to Alzheimer's disease.

Hum Brain Mapp 2020 Jul 9. Epub 2020 Jul 9.

Computational, Cognitive & Clinical Neuroimaging Laboratory, Department of Brain Sciences, Imperial College London, London, UK.

Multiple biomarkers can capture different facets of Alzheimer's disease. However, statistical models of biomarkers to predict outcomes in Alzheimer's rarely model nonlinear interactions between these measures. Here, we used Gaussian Processes to address this, modelling nonlinear interactions to predict progression from mild cognitive impairment (MCI) to Alzheimer's over 3 years, using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Read More

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http://dx.doi.org/10.1002/hbm.25133DOI Listing

Understanding cause and effect in Alzheimer's pathophysiology: implications for clinical trials.

Neuropathol Appl Neurobiol 2020 Jul 8. Epub 2020 Jul 8.

Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Faculty of Medicine, Southampton, United Kingdom.

Alzheimer's disease (AD) pathology is multi-faceted, including extracellular accumulation of amyloid-β (Aβ), accumulation of tau within neurons, glial activation and loss of neurons and synapses. From a neuropathological perspective, usually at a single time-point and often at the end-stage of the disease, it is challenging to understand the cause and effect relationships between these components. There are at least four ways of trying to unravel these relationships. Read More

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http://dx.doi.org/10.1111/nan.12642DOI Listing

CEOT Variants or Entities: Time for a Rethink? A Case Series with Review of the Literature.

Head Neck Pathol 2020 Jul 8. Epub 2020 Jul 8.

Unit of Oral and Maxillofacial Medicine, Pathology and Surgery, School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield, S10 2TA, UK.

The first detailed description of calcifying epithelial odontogenic tumor (CEOT) are ascribed to Jens Pindborg, but this tumor was described some years previously. Subsequently, CEOT was included in the 1971 WHO classification of odontogenic tumors and a since then number of variants have been described, which have added confusion to the diagnostic criteria. We aimed to survey the literature on the variants of CEOT, in parallel with a review of our single institution experience of CEOTs. Read More

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http://dx.doi.org/10.1007/s12105-020-01200-9DOI Listing

Altered age-linked regulation of plasma DYRK1A in elderly cognitive complainers (INSIGHT-preAD study) with high brain amyloid load.

Alzheimers Dement (N Y) 2020 2;6(1):e12046. Epub 2020 Jul 2.

INSERM U 1127, CNRS UMR 7225 UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et la Moelle épinière, ICM Sorbonne Universités Paris France.

Introduction: An effective therapy has not yet been developed for Alzheimer's disease (AD), in part because pathological changes occur years before clinical symptoms manifest. We recently showed that decreased plasma DYRK1A identifies individuals with mild cognitive impairment (MCI) or AD, and that aged mice have higher DYRK1A levels.

Methods: We assessed DYRK1A in plasma in young/aged controls and in elderly cognitive complainers with low (L) and high (H) brain amyloid load. Read More

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http://dx.doi.org/10.1002/trc2.12046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331462PMC

Sputum and serum autoantibody profiles and their clinical correlation patterns in COPD patients with and without eosinophilic airway inflammation.

J Thorac Dis 2020 Jun;12(6):3085-3100

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Autoimmunity plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the autoantibody responses and their clinical correlation patterns in COPD patients with and without airway eosinophilic inflammation are unknown. The aim of this study was to compare the autoantibody profiles and their clinical associations in stable COPD patients, stratified by airway inflammatory phenotypes. Read More

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http://dx.doi.org/10.21037/jtd-20-545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330801PMC

Peroxisome Proliferator-activated Receptor (PPAR)-γ Modifies Aβ Neurotoxin-induced Electrophysiological Alterations in Rat Primary Cultured Hippocampal Neurons.

Iran J Pharm Res 2019 ;18(3):1403-1418

Neuroscience Research Center, Department of Physiology, School of Medical, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Alzheimer's disease (AD) is undoubtedly one of the serious and growing public health challenges in the world today. There is an unmet need for new and effective preventative and therapeutic treatment approaches for AD, particularly at early stages of the disease. However, the underlying mechanism against Aβ-induced electrophysiological alteration in cultured hippocampal pyramidal neurons is still not fully understood. Read More

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http://dx.doi.org/10.22037/ijpr.2019.1100783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934959PMC
January 2019

Synthesis and Biological Assessment of 2-Hydroxyiminoethanones as Anti-Inflammatory and β-Amyloid Aggregation Inhibitors.

Iran J Pharm Res 2019 ;18(3):1288-1298

Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Alzheimer's disease (AD) is a neuroinflammatory based pathologic state in which β-amyloid aggregates are major devastating agents. In this study, a series of 2-hydroxyiminoethanones were synthesized and evaluated as anti-inflammatory in carrageenan and formalin tests and inhibitors of β-amyloid aggregation. Compounds were synthesized through a two-step reaction. Read More

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http://dx.doi.org/10.22037/ijpr.2019.15567.13181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934981PMC
January 2019