85,468 results match your criteria Amyloid [Journal]


Serum amyloid a as an indicator of impending xenograft failure: Experimental studies.

Int J Surg 2018 Dec 3. Epub 2018 Dec 3.

Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

Background: There is well-documented systemic inflammatory response in xenograft recipients to the presence of a pig graft. Serum amyloid A (SAA) is an inflammatory marker that is elevated in various pathological states. The assay used to measure it is (i) simple, (ii) relatively inexpensive, and (iii) provides an answer within minutes. Read More

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December 2018
4 Reads

Amyloid-degrading enzymes in Alzheimer´s disease: from molecules to genetic therapy

Rev Med Inst Mex Seguro Soc 2018 11 30;56(4):387-394. Epub 2018 Nov 30.

Universidad Autónoma de Campeche, Facultad de Ciencias Químico Biológicas, Cuerpo Académico Ciencias de la Salud y Biotecnología. Campeche, Campeche, México

Alzheimer’s disease (AD) is the main form of dementia in elderly population worldwide. By 2010 it was estimated that 35.6 million of people were living with this disease, and it was projected that this figure will triple by the year 2050. Read More

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November 2018
2 Reads

Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5.

PLoS One 2018 6;13(12):e0208440. Epub 2018 Dec 6.

Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.

Intracellular inclusions of aggregated tau appear in neurons and glial cells in a range of neurodegenerative diseases known as tauopathies. Inhibition of pathological changes in tau is a therapeutic target for tauopathy. We recently synthesized a novel curcumin derivative, named Shiga-Y5, and showed that Shiga-Y5 inhibited cognitive impairment and amyloid deposition in a mouse model of Alzheimer's disease. Read More

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December 2018
2 Reads

Predicting Progression to Mild Cognitive Impairment.

Ann Neurol 2018 Dec 6. Epub 2018 Dec 6.

Department of Radiology, Mayo Clinic, Rochester, MN, USA.

Despite much attention to the use of biomarkers for predicting Alzheimer's disease, little information is available at the individual level. We used the population-based Mayo Clinic Study of Aging to estimate absolute risk of cognitive impairment by biomarker group. Risk increased with age and any biomarker abnormality. Read More

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December 2018
1 Read

Levels of 17β-hydroxysteroid dehydrogenase type 10 in CSF are not a valuable biomarker for multiple sclerosis.

Biomark Med 2018 Dec 6. Epub 2018 Dec 6.

National Institute of Mental Health, 250 67 Klecany, Czech Republic.

Aim: We aimed to characterize the role of mitochondrial 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) overexpression in multiple sclerosis (MS) and to evaluate its use as a biomarker. Materials & methods: We estimated levels of 17β-HSD10, amyloid β 1-42, cyclophilin D, 17β-HSD10-cyclophilin D complexes or 17β-HSD10-parkin complexes in cerebrospinal fluid (CSF) samples.

Results: The increase in 17β-HSD10 levels or in 17β-HSD10-parkin complexes and links to leukocytes were found only in relapsing-remitting MS. Read More

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December 2018

The folding and aggregation energy landscapes of tethered RRM domains of human TDP-43 are coupled via a metastable molten globule-like oligomer.

Biochemistry 2018 Dec 6. Epub 2018 Dec 6.

Stress-induced misfolding and intraneuronal aggregation of the highly conserved nucleic acid binding protein TDP-43 (transactive response DNA binding protein 43 kDa) and its fragments have been implicated in amyotrophic lateral sclerosis and multiple other neurodegenerative diseases. However, the physico-chemical mechanism of its misfolding from the functional folded state is poorly understood. TDP-43 is a four domain protein and it performs the essential nucleic acid binding function with the help of its two tandem RNA recognition motif domains naturally tethered by a linker (called here tethered RRM domain of TDP-43 or TDP-43). Read More

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December 2018

Influence of dietary restriction and low-intensity exercise on weight loss and insulin sensitivity in obese equids.

J Vet Intern Med 2018 Dec 5. Epub 2018 Dec 5.

Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Werribee, Victoria, Australia.

Background: The importance of including exercise with dietary modification for the management of obese equids is not clearly understood.

Objectives: To evaluate the effect of a practical low-intensity exercise regimen, in addition to dietary restriction, on indices of insulin sensitivity (SI) and plasma adipokine concentrations in obese equids.

Animals: Twenty-four obese (body condition score [BCS] ≥ 7/9) horses and ponies. Read More

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December 2018
2 Reads

Mouse models of Alzheimer's disease cause rarefaction of pial collaterals and increased severity of ischemic stroke.

Angiogenesis 2018 Dec 5. Epub 2018 Dec 5.

Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 6309 MBRB, Chapel Hill, NC, 27599-7545, USA.

Vascular dysfunction contributes to the progression and severity of Alzheimer's disease (AD). Patients with AD also sustain larger infarctions after ischemic stroke; however, the responsible mechanisms are unknown. Pial collaterals are the primary source of protection in stroke. Read More

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December 2018

Centiloid scaling for quantification of brain amyloid with [F]flutemetamol using multiple processing methods.

EJNMMI Res 2018 Dec 5;8(1):107. Epub 2018 Dec 5.

Imaging Technology Group, GE Healthcare, The Grove Centre, White Lion Road, Amersham, Buckinghamshire, UK.

Introduction: A standardised method for quantifying β-amyloid PET tracers would allow comparison across different tracers and different sites. The development of the Centiloid scale has aimed to achieve this, applying a common scale to better aid the diagnosis and prognosis of Alzheimer's disease (AD) and to monitor anti-amyloid therapeutic interventions. Here, we apply the Centiloid method to [F]flutemetamol and [C]PiB (PiB, Pittsburgh compound B) PET images and derive the scaling factor to express their binding in Centiloids. Read More

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December 2018

Synthesis and biochemical characterization of quasi-stable trimer models of full-length amyloid β40 with a toxic conformation.

Chem Commun (Camb) 2018 Dec 6. Epub 2018 Dec 6.

Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.

Here, we report the first synthesis of quasi-stable trimer models of full-length Aβ40 with a toxic conformation using a 1,3,5-phenyltris-l-alanyl linker at position 34, 36, or 38. The only trimer to exhibit weak neurotoxicity against SH-SY5Y cells was the one which was linked at position 38. This suggests that such a propeller-type trimer model is not prone to forming oligomers with potent neurotoxicity, which is in contrast with its corresponding dimer model. Read More

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December 2018
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Cerebrospinal fluid neurogranin/β-site APP-cleaving enzyme 1 predicts cognitive decline in preclinical Alzheimer's disease.

Alzheimers Dement (N Y) 2018 10;4:617-627. Epub 2018 Nov 10.

Department of Neurology, Akershus University Hospital, Lørenskog, Norway.

Introduction: The cerebrospinal fluid neurogranin (Ng)/β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) ratio may reflect synaptic affection resulting from reduced beta-amyloid (Aβ) clearance. We hypothesize that increased Ng/BACE1 ratio predicts the earliest cognitive decline in Alzheimer's disease.

Methods: We compared Ng/BACE1 levels between cases with subjective cognitive decline (n = 18) and mild cognitive impairment (n = 20) both with amyloid plaques and healthy controls (-ε4+, n = 16; -ε4-, n = 20). Read More

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November 2018
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Amyloid Imaging.

Authors:
Jessica Williams

J Nucl Med Technol 2018 Dec;46(4):341-342

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December 2018

Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β Induced Synaptic Dysfunction and Loss.

J Neurosci 2018 Dec 5. Epub 2018 Dec 5.

Cellular Neuroscience, Neurodegeneration & Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT USA 06536.

Dozens of genes have been implicated in Late Onset Alzheimer's Disease (AD) risk, but none have a defined mechanism of action in neurons. Here, we show that the risk factor Pyk2 (PTK2B) localizes specifically to neurons in adult brain. Absence of Pyk2 has no major effect on synapse formation nor the basal parameters of synaptic transmission in the hippocampal Schaffer collateral pathway. Read More

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December 2018
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Age-dependent behavioral and biochemical characterization of single APP knock-in mouse (APP) model of Alzheimer's disease.

Neurobiol Aging 2018 Nov 5;75:25-37. Epub 2018 Nov 5.

Canadian Center for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada. Electronic address:

Saito et al developed a novel amyloid precursor protein (APP) knock-in mouse model (APP) for Alzheimer's disease (AD) to overcome the problem of overexpression of APP in available transgenic mouse models. However, this new mouse model for AD is not fully characterized age-dependently with respect to behavioral and biochemical changes. Therefore, in the present study, we performed an age-dependent behavioral and biochemical characterization of this newly developed mouse model. Read More

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November 2018

Distinct functional roles of Vps41-mediated neuroprotection in Alzheimer's and Parkinson's disease models of neurodegeneration.

Hum Mol Genet 2018 Dec;27(24):4176-4193

Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA.

Commonalities and, in some cases, pathological overlap between neurodegenerative diseases have led to speculation that targeting of underlying mechanisms might be of potentially shared therapeutic benefit. Alzheimer's disease is characterized by the formation of plaques, composed primarily of the amyloid-β 1-42 (Aβ) peptide in the brain, resulting in neurodegeneration. Previously, we have shown that overexpression of the lysosomal-trafficking protein, human Vps41 (hVps41), is neuroprotective in a transgenic worm model of Parkinson's disease, wherein progressive dopaminergic neurodegeneration is induced by α-synuclein overexpression. Read More

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December 2018

Association of Cerebrospinal Fluid Neurofilament Light Protein Levels With Cognition in Patients With Dementia, Motor Neuron Disease, and Movement Disorders.

JAMA Neurol 2018 Dec 3. Epub 2018 Dec 3.

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.

Importance: Neuronal and axonal destruction are hallmarks of neurodegenerative diseases, but it is difficult to estimate the extent and progress of the damage in the disease process.

Objective: To investigate cerebrospinal fluid (CSF) levels of neurofilament light (NFL) protein, a marker of neuroaxonal degeneration, in control participants and patients with dementia, motor neuron disease, and parkinsonian disorders (determined by clinical criteria and autopsy), and determine its association with longitudinal cognitive decline.

Design, Setting, And Participants: In this case-control study, we investigated NFL levels in CSF obtained from controls and patients with several neurodegenerative diseases. Read More

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December 2018

Correlation of In Vivo [18F]Flortaucipir With Postmortem Alzheimer Disease Tau Pathology.

JAMA Neurol 2018 Dec 3. Epub 2018 Dec 3.

Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.

Importance: In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Read More

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December 2018

Classification of amyloid PET images using novel features for early diagnosis of Alzheimer's disease and mild cognitive impairment conversion.

Nucl Med Commun 2018 Nov 29. Epub 2018 Nov 29.

Department of Engineering Science, University of Oxford, Oxford.

Background: New PET tracers could have a substantial impact on the early diagnosis of Alzheimer's disease (AD), particularly if they are accompanied by optimised image analysis and machine learning methods. Fractal dimension (FD) analysis, a measure of shape complexity, has been proven useful in MRI but its application to fluorine-18 amyloid PET has not yet been demonstrated. Shannon entropy (SE) has also been proposed as a measure of image complexity in DTI imaging, but it is not yet widely used in radiology. Read More

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November 2018

Tau Abnormalities and the Potential Therapy in Alzheimer's Disease.

J Alzheimers Dis 2018 Nov 29. Epub 2018 Nov 29.

The Institute of Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, P.R. China.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that is characterized by progressive memory loss and two main pathological hallmarks, including the extracellular amyloid plaques and intracellular neurofibrillary tangles. The microtubule-related protein tau is involved in the pathogenesis of many neurological diseases commonly known as tauopathies and is found to be abnormally hyperphosphorylated in AD and accumulated in neurons. Besides hyperphosphorylation, tau also undergoes abnormal glycosylation, ubiquitination, glycation, and other posttranslational modifications. Read More

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November 2018
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Increased Hyaluronan and TSG-6 in Association with Neuropathologic Changes of Alzheimer's Disease.

J Alzheimers Dis 2018 Nov 29. Epub 2018 Nov 29.

Department of Pathology, Division of Neuropathology, University of Washington, Seattle, WA, USA.

Little is known about the extracellular matrix (ECM) during progression of AD pathology. Brain ECM is abundant in hyaluronan (HA), a non-sulfated glycosaminoglycan synthesized by HA synthases (HAS) 1-3 in a high molecular weight (MW) form that is degraded into lower MW fragments. We hypothesized that pathologic severity of AD is associated with increases in HA and HA-associated ECM molecules. Read More

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November 2018

Evaluation of Ocular Perfusion in Alzheimer's Disease Using Optical Coherence Tomography Angiography.

J Alzheimers Dis 2018 Nov 26. Epub 2018 Nov 26.

Department of Ophthalmology, University of Muenster Medical Center, Muenster, Germany.

Background: There is increasing evidence for the involvement of cerebrovascular factors in Alzheimer's disease (AD).

Objective: To evaluate retinal and optic nerve head perfusion in patients with AD using optical coherence tomography angiography (OCTA), and to analyze the correlations of quantitative OCTA metrics with AD pathology and vascular cerebral lesions in AD patients.

Methods: 36 eyes of 36 patients with AD (study group) and 38 eyes of 38 healthy subjects (control group) were prospectively included in this study. Read More

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November 2018

Tocotrienol Rich Fraction Supplementation Modulate Brain Hippocampal Gene Expression in APPswe/PS1dE9 Alzheimer's Disease Mouse Model.

J Alzheimers Dis 2018 Nov 28. Epub 2018 Nov 28.

Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive abilities. AD is associated with aggregation of amyloid-β (Aβ) deposited in the hippocampal brain region. Our previous work has shown that tocotrienol rich fraction (TRF) supplementation was able to attenuate the blood oxidative status, improve behavior, and reduce fibrillary-type Aβ deposition in the hippocampus of an AD mouse model. Read More

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November 2018

Amyloid precursor protein and amyloid precursor-like protein 2 have distinct roles in modulating myelination, demyelination, and remyelination of axons.

Glia 2018 Dec 2. Epub 2018 Dec 2.

Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.

The identification of factors that regulate myelination provides important insight into the molecular mechanisms that coordinate nervous system development and myelin regeneration after injury. In this study, we investigated the role of amyloid precursor protein (APP) and its paralogue amyloid precursor-like protein 2 (APLP2) in myelination using APP and APLP2 knockout (KO) mice. Given that BACE1 regulates myelination and myelin sheath thickness in both the peripheral and central nervous systems, we sought to determine if APP and APLP2, as alternate BACE1 substrates, also modulate myelination, and therefore provide a better understanding of the events regulating axonal myelination. Read More

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December 2018

Aberrant accrual of BIN1 near Alzheimer's disease amyloid deposits in transgenic models.

Brain Pathol 2018 Nov 30. Epub 2018 Nov 30.

Department of Neurobiology, The University of Chicago, Chicago, IL, USA.

BIN1 is the most significant late-onset Alzheimer's Disease (AD) susceptibility locus identified via genome-wide association studies. BIN1 is an adaptor protein that regulates membrane dynamics in the context of endocytosis and membrane remodeling. An increase in BIN1 expression and changes in the relative levels of alternatively-spliced BIN1 isoforms have been reported in the brains of patients with AD. Read More

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November 2018
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Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives.

Acta Pharm Sin B 2018 Oct 18;8(6):862-880. Epub 2018 May 18.

Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Gyeonggi-do 14662, Republic of Korea.

Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Read More

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October 2018
2 Reads

CSF β-amyloid and risk of freezing of gait in early Parkinson disease.

Neurology 2018 Nov 30. Epub 2018 Nov 30.

From the Department of Neurology (R.K., H.-J.K., A.K., B.J.), Seoul National University Hospital, College of Medicine; Department of Neurology (R.K.), Aerospace Medical Center, Republic of Korea Air Force, Cheongju; Medical Research Collaborating Center (J.L.), Seoul National University Hospital; Department of Neurology (M.J.), Presbyterian Medical Center, Jeonju, Republic of Korea; and Department of Neurology (U.J.K.), Columbia University Medical Center, New York, NY.

Objective: To determine whether CSF biomarkers can be used as a predictor of freezing of gait (FOG) in Parkinson disease (PD) and to investigate the predictive value of clinical, dopamine transporter (DAT) imaging, and CSF parameters both separately and in combination.

Methods: This study using the PPMI data included 393 patients with newly diagnosed PD without FOG at baseline. We evaluated CSF for β-amyloid 1-42 (Aβ), α-synuclein, total tau, phosphorylated tau, and the calculated ratio of Aβ to total tau at baseline. Read More

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November 2018

Structural progression of amyloid-β Arctic mutant aggregation in cells revealed by multi-parametric imaging.

J Biol Chem 2018 Nov 30. Epub 2018 Nov 30.

Chemical Engineering and Biotechnology, University of Cambridge, United Kingdom.

The 42-amino-acid amyloid-β (Aβ42) is a critical causative agent in the pathology of Alzheimer's disease. The hereditary Arctic mutation of Aβ42 (E22G) leads to increased intracellular accumulation of amyloid-β in early-onset AD. However, it remains largely unknown how the Arctic mutant variant leads to aggressive protein aggregation and increased intracellular toxicity. Read More

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November 2018

Beneficial effect of ovocystatin on the cognitive decline in APP/PS1 transgenic mice.

Adv Med Sci 2018 Nov 29;64(1):65-71. Epub 2018 Nov 29.

Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.

Purpose: Cystatin C plays an important role in the course of neurodegenerative diseases and has a beneficial effect through inhibiting cysteine proteases and amyloid-β aggregation. It also induces proliferation and autophagy. Cystatin isolated from chicken egg white, called ovocystatin, has been widely used in the medical and pharmaceutical research due to its structural and biological similarities to human cystatin C. Read More

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November 2018

Neural substrates of cognitive reserve in Alzheimer's disease spectrum and normal aging.

Neuroimage 2018 Nov 29. Epub 2018 Nov 29.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; KI for Health Science and Technology, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address:

The concept of cognitive reserve (CR) originated from discrepancies between the degree of brain pathology and the severity of clinical manifestations. CR has been characterized through CR proxies, such as education and occupation complexity; however, such approaches have inherent limitations. Although several methods have been developed to overcome these limitations, they fail to reflect the entire Alzheimer's disease (AD) pathology. Read More

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November 2018
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Progressive circuit resistance training improves inflammatory biomarkers and insulin resistance in obese men.

Physiol Behav 2018 Nov 29. Epub 2018 Nov 29.

Univ Rennes, M2S (Laboratoire Mouvement, Sport, Santé) - EA 1274, F-35000 Rennes, France. Electronic address:

Background: Circuit resistance training (CRT) is a time-efficient exercise modality for improving skeletal muscle and cardiovascular fitness. But the beneficial role of CRT in obese individuals is still not well understood. This study explores the reducing effects of progressive CRT on inflammatory biomarkers and cardiometabolic risk factors in obese young men. Read More

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November 2018
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Cooperative Induction of Ordered Peptide and Fatty Acid Aggregates.

Biophys J 2018 Nov 10. Epub 2018 Nov 10.

Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, Zürich, Switzerland. Electronic address:

Interactions between biological membranes and disease-associated amyloids are well documented, and their prevalence suggests that an inherent affinity exists between these molecular assemblies. Our interest in the molecular origins of life have led us to investigate the nature of such interactions in the context of their molecular predecessors (i.e. Read More

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November 2018
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Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer's disease.

J Neuroimmunol 2018 Nov 20;326:62-74. Epub 2018 Nov 20.

Department of Pharmacology, SPP School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India. Electronic address:

Microglial activation is a distinguished attribute in many neurodegenerative diseases of aging. Compelling evidence suggests that neuroinflammation stimulated by microglia, the resident macrophage-like immune cells in the brain, play a contributing role in the pathogenesis of Alzheimer's disease (AD). Postmortem brain tissue of individuals with AD has credibly demonstrated that neuroinflammation is likely to be a key driver of the disease. Read More

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November 2018

Inhibitors of Aβ42-induced endoplasmic reticular unfolded protein response (UPR), in yeast, also rescue yeast cells from Aβ42-mediated apoptosis.

Eur J Pharm Sci 2018 Nov 28. Epub 2018 Nov 28.

Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK. Electronic address:

Aggregated Aβ peptides which cause amyloid deposits, a characteristic of Alzheimer's disease (AD), activate a stress response in the endoplasmic reticulum (ER), known as the unfolded protein response, UPR. Nascent UPR induction helps in reducing ER stress by eliminating accumulated misfolded/aggregated secretory proteins. However, prolonged UPR induction may trigger apoptosis. Read More

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November 2018

Nucleation of β-rich oligomers and β-barrels in the early aggregation of human islet amyloid polypeptide.

Biochim Biophys Acta Mol Basis Dis 2018 Nov 28. Epub 2018 Nov 28.

Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA. Electronic address:

The self-assembly of human islet amyloid polypeptide (hIAPP) into β-sheet rich amyloid aggregates is associated with pancreatic β-cell death in type 2 diabetes (T2D). Prior experimental studies of hIAPP aggregation reported the early accumulation of α-helical intermediates before the rapid conversion into β-sheet rich amyloid fibrils, as also corroborated by our experimental characterizations with transmission electron microscopy and Fourier transform infrared spectroscopy. Although increasing evidence suggests that small oligomers populating early hIAPP aggregation play crucial roles in cytotoxicity, structures of these oligomer intermediates and their conformational conversions remain unknown, hindering our understanding of T2D disease mechanism and therapeutic design targeting these early aggregation species. Read More

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November 2018
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Quantitative proteomics reveals distinct composition of amyloid plaques in Alzheimer's disease.

Alzheimers Dement 2018 Nov 28. Epub 2018 Nov 28.

Department of Human Anatomy, Histology and Embryology, Neuroscience Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Electronic address:

Introduction: We investigated the proteomic profiles of amyloid plaques (APs) from Alzheimer's disease (AD) and age-matched non-AD brains and APP/PS1 transgenic model mice.

Methods: APs and adjacent control regions were collected from fresh-frozen brain sections using laser capture dissection. Proteins were quantitated using tag-labeling coupled high-throughput mass spectra. Read More

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November 2018

Cerebrospinal fluid biomarkers of neurofibrillary tangles and synaptic dysfunction are associated with longitudinal decline in white matter connectivity: A multi-resolution graph analysis.

Neuroimage Clin 2018 Oct 23. Epub 2018 Oct 23.

Department of Biostatistics and Medical Informatics, University of Wisconsin - Madison, Madison, WI, USA; Department of Computer Science, University of Wisconsin - Madison, Madison, WI, USA.

In addition to the development of beta amyloid plaques and neurofibrillary tangles, Alzheimer's disease (AD) involves the loss of connecting structures including degeneration of myelinated axons and synaptic connections. However, the extent to which white matter tracts change longitudinally, particularly in the asymptomatic, preclinical stage of AD, remains poorly characterized. In this study we used a novel graph wavelet algorithm to determine the extent to which microstructural brain changes evolve in concert with the development of AD neuropathology as observed using CSF biomarkers. Read More

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October 2018

IL1-blocking therapy in colchicine-resistant familial Mediterranean fever.

Eur J Rheumatol 2018 Dec 12;5(4):230-234. Epub 2018 Oct 12.

Division of Rheumatology, Department of Internal Medicine, Heidelberg University Hospital, Heidelberg, Germany.

Objective: Approximately 10%-20% of patients with familial Mediterranean fever (FMF) show an inadequate response to colchicine. In our cohort study, patients with FMF with or without amyloidosis and with an inadequate response to colchicine were treated with anakinra or canakinumab.

Methods: Clinical and laboratory parameters, Mediterranean fever (MEFV) mutations, and patient-reported outcomes were analyzed in 31 patients treated with anakinra or canakinumab. Read More

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December 2018

Lipocalin 2 contributes to brain iron dysregulation but does not affect cognition, plaque load, and glial activation in the J20 Alzheimer mouse model.

J Neuroinflammation 2018 Nov 30;15(1):330. Epub 2018 Nov 30.

Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, Groningen, 9747 AG, The Netherlands.

Background: Lipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions. Interestingly, both neuroprotective and neurodegenerative effects have been described for Lcn2. Increased Lcn2 levels were found in human post-mortem Alzheimer (AD) brain tissue, and in vitro studies indicated that Lcn2 aggravates amyloid-β-induced toxicity. Read More

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November 2018

Recent advances in multi-target anti-Alzheimer disease compounds (2013 up to present).

Curr Med Chem 2018 Dec 3. Epub 2018 Dec 3.

Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo 315211. China.

Since the last century, when scientists proposed the lock-and-key model, the discovery of drugs has focused on the development of drugs acting on single target. However, single-target drug therapies are not effective to complex diseases with multi-factorial pathogenesis. Moreover, the combination of single-target drugs readily causes drug resistance and side effects. Read More

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December 2018

Pharmacokinetics and acetylcholine releasing effects of ginsenoside Rg1 in hippocampus of beta-amyloid model rats.

J Asian Nat Prod Res 2018 Dec 3:1-10. Epub 2018 Dec 3.

b Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology , Beijing Hospital , Bejing 100044 , China.

This study aimed at investigating the pharmacokinetics (PK) and acetylcholine (Ach) releasing effects of ginsenoside Rg1 in hippocampus (HIP) of soluble oligomeric assemblies of amyloid beta (ADDLs) induced Alzheimer's disease (AD) model rats. Extracellular fluid was collected by microdialysis technique. The concentrations of Rg1 and Ach in dialysates were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Read More

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December 2018

Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer's Disease?

Ann Otol Rhinol Laryngol 2018 Dec 2:3489418814865. Epub 2018 Dec 2.

1 University of São Paulo, São Paulo, Brazil.

Objectives:: The clinical symptoms of Alzheimer's disease (AD) are preceded by a long asymptomatic period associated with "silent" deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. Read More

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December 2018

Dual-aptamers-conjugated molecular modulator for detecting bioactive metal ions and inhibiting metal-mediated protein aggregation.

Anal Chem 2018 Dec 3. Epub 2018 Dec 3.

Bioactive metal ions play important roles in both physiological and pathological processes. Developing biosensing probes for bioactive metal ions detection can contribute to fields including disease diagnosis/therapy and studying the mechanisms of bio-logical activities. In this work, we designed a dual-aptamers-conjugated molecular modulator that can detect Zn2+ and further inhibit Zn2+-induced Amyloid β (Aβ) aggregation. Read More

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December 2018

Improving the Gene Ontology Resource to Facilitate More Informative Analysis and Interpretation of Alzheimer's Disease Data.

Genes (Basel) 2018 Nov 29;9(12). Epub 2018 Nov 29.

UCL Institute of Cardiovascular Science, University College London, Rayne Building, 5 University Street, London WC1E 6JF, UK.

The analysis and interpretation of high-throughput datasets relies on access to high-quality bioinformatics resources, as well as processing pipelines and analysis tools. Gene Ontology (GO, geneontology.org) is a major resource for gene enrichment analysis. Read More

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November 2018

Toward Exosome-Based Neuronal Diagnostic Devices.

Micromachines (Basel) 2018 Nov 29;9(12). Epub 2018 Nov 29.

Department of Electrical Engineering, Kwangwoon University, 447-1 Wolgye, Nowon, Seoul 01897, Korea.

Targeting exosome for liquid biopsy has gained significant attention for its diagnostic and therapeutic potential. For detecting neuronal disease diagnosis such as Alzheimer's disease (AD), the main technique for identifying AD still relies on positron-emission tomography (PET) imaging to detect the presence of amyloid-β (Aβ). While the detection of Aβ in cerebrospinal fluid has also been suggested as a marker for AD, the lack of quantitative measurements has compromised existing assays. Read More

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November 2018

Iso-α-Acids, the Bitter Components of Beer, Suppress Microglial Inflammation in rTg4510 Tauopathy.

Molecules 2018 Nov 29;23(12). Epub 2018 Nov 29.

Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan.

Due to the growth in aging populations, prevention for cognitive decline and dementia are in great demand. We previously demonstrated that the consumption of iso-α-acids (IAA), the hop-derived bitter compounds in beer, prevents inflammation and Alzheimer's disease pathology in model mice. However, the effects of iso-α-acids on inflammation induced by other agents aside from amyloid β have not been investigated. Read More

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November 2018

Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding.

PLoS One 2018 5;13(12):e0208358. Epub 2018 Dec 5.

Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.

Background: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer's disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies. Read More

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December 2018

Amyloid β-induced elevation of O-GlcNAcylated c-Fos promotes neuronal cell death.

Aging Cell 2018 Dec 4:e12872. Epub 2018 Dec 4.

Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Korea.

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive memory loss resulting from cumulative neuronal cell death. O-linked β-N-acetyl glucosamine (O-GlcNAc) modification of the proteins reflecting glucose metabolism is altered in the brains of patients with AD. However, the link between altered O-GlcNAc modification and neuronal cell death in AD is poorly understood. Read More

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December 2018

Nurr1 (NR4A2) regulates Alzheimer's disease-related pathogenesis and cognitive function in the 5XFAD mouse model.

Aging Cell 2018 Dec 4:e12866. Epub 2018 Dec 4.

Molecular Neurobiology Laboratory, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts.

The orphan nuclear receptor Nurr1 (also known as NR4A2) is critical for the development and maintenance of midbrain dopaminergic neurons, and is associated with Parkinson's disease. However, an association between Nurr1 and Alzheimer's disease (AD)-related pathology has not previously been reported. Here, we provide evidence that Nurr1 is expressed in a neuron-specific manner in AD-related brain regions; specifically, it is selectively expressed in glutamatergic neurons in the subiculum and the cortex of both normal and AD brains. Read More

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December 2018
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Dynamin-related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases.

J Cell Physiol 2018 Dec 4. Epub 2018 Dec 4.

Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China.

Mitochondria play a key role in the maintenance of neuronal function by continuously providing energy. Here, we will give a detailed review about the recent developments in regards to dynamin-related protein 1 (Drp1) induced unbalanced mitochondrial dynamics, excessive mitochondrial division, and neuronal injury in neural system dysfunctions and neurodegenerative diseases, including the Drp1 knockout induced mice embryonic death, the dysfunction of the Drp1-dependent mitochondrial division induced neuronal cell apoptosis and impaired neuronal axonal transportation, the abnormal interaction between Drp1 and amyloid β (Aβ) in Alzheimer's disease (AD), the mutant Huntingtin (Htt) in Huntington's disease (HD), and the Drp1-associated pathogenesis of other neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Drp1 is required for mitochondrial division determining the size, shape, distribution, and remodeling as well as maintaining of mitochondrial integrity in mammalian cells. Read More

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December 2018

Curcumin and a hemi-analogue with improved blood-brain barrier permeability protect against amyloid-beta toxicity in Caenorhabditis elegans via SKN-1/Nrf activation.

J Pharm Pharmacol 2018 Dec 4. Epub 2018 Dec 4.

School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.

Objectives: This study aims to investigate the blood-brain barrier (BBB) permeability of curcumin analogues with shortened linkers and their ability to protect against amyloid-beta toxicity in a whole organism model.

Method: Four curcumin analogues were synthesized. These analogues and curcumin were evaluated for their BBB permeability in the parallel artificial membrane permeability assay. Read More

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December 2018