100,163 results match your criteria Alzheimer Disease


Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of Alzheimer's disease.

Exp Gerontol 2019 Feb 17. Epub 2019 Feb 17.

Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, Japan.

Systemic organ dysfunction is one of the important issues for the patients with Alzheimer's disease (AD) and their caregivers. Recent evidences suggest that periodontitis is a possible risk factor for progression of AD and lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) which is a major periodontopathic bacteria induces cognitive impairment in mice. However, the precise relationships between the brain exposure of Pg-LPS and systemic organ dysfunction in AD patients are still undetermined. Read More

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http://dx.doi.org/10.1016/j.exger.2019.02.007DOI Listing
February 2019

Trans ε viniferin decreases amyloid deposits and inflammation in a mouse transgenic Alzheimer model.

PLoS One 2019 20;14(2):e0212663. Epub 2019 Feb 20.

University of Poitiers, EA3808 Neurovascular Unit and Cognitive Disorders, Pôle Biologie Santé, POITIERS, France.

As Alzheimer's disease (AD) induces several cellular and molecular damages, it could be interesting to use multi-target molecules for therapeutics. We previously published that trans ε-viniferin induced the disaggregation of Aβ42 peptide and inhibited the inflammatory response in primary cellular model of AD. Here, effects of this stilbenoid were evaluated in transgenic APPswePS1dE9 mice. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212663PLOS
February 2019
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Japanese Old Stories Cognitive Scale: a screening test to detect cognitive disease and prompt visiting a memory clinic.

Psychogeriatrics 2019 Feb 20. Epub 2019 Feb 20.

Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, Toyoake, Japan.

Background: Early detection and diagnosis is critical in enhancing treatment outcomes for those with cognitive disease. However, most Japanese patients are averse to visiting mental health clinics or taking cognitive screening examinations. A new simple screening test is needed that is acceptable to patients and encourages them to visit a memory clinic if indicated. Read More

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http://dx.doi.org/10.1111/psyg.12398DOI Listing
February 2019

Fibroblast growth factor 21 ameliorates neurodegeneration in rat and cellular models of Alzheimer's disease.

Redox Biol 2019 Feb 1;22:101133. Epub 2019 Feb 1.

Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

Our understanding of the mechanisms underlying process in Alzheimer's disease (AD) is far from completion and new therapeutic targets are urgently needed. Recently, the link between dementia and diabetes mellitus (DM) prompted us to search for new therapeutic strategies from glucose metabolism regulators for neurodegeneration. Previous studies have indicated that fibroblast growth factor 21 (FGF21), an attractive and potential therapeutic treatment for DM, may exert diverse effects in the central nervous system. Read More

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http://dx.doi.org/10.1016/j.redox.2019.101133DOI Listing
February 2019

Fine-tuning the neuroprotective and blood-brain barrier permeability profile of multi-target agents designed to prevent progressive mitochondrial dysfunction.

Eur J Med Chem 2019 Feb 6;167:525-545. Epub 2019 Feb 6.

CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal. Electronic address:

Alzheimer's disease is an irreversible, complex and progressive neurodegenerative disorder associated with oxidative stress and mitochondrial dysfunction. Exogenous antioxidants can be beneficial for decreasing oxidative stress, as they are able to reward the lack of efficacy of the endogenous defense systems and raise the overall antioxidant response in a pathological condition. Along our overarching project related with the design and development of potent and safe multi-target mitochondriotropic antioxidants, based on dietary antioxidants, novel derivatives were obtained. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.01.055DOI Listing
February 2019

Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer's disease.

Eur J Med Chem 2019 Feb 14;167:510-524. Epub 2019 Feb 14.

Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India. Electronic address:

The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N-benzylpiperidine analogs (17-31 and 32-46) were designed and synthesized as multi-functional inhibitors of acetylcholinesterase (AChE) and β-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.02.030DOI Listing
February 2019

Is there a specific memory signature associated with Aβ-PET positivity in patients with amnestic mild cognitive impairment?

Neurobiol Aging 2019 Jan 31;77:94-103. Epub 2019 Jan 31.

Inserm, Inserm UMR-S U1237, Université de Caen-Normandie, GIP Cyceron, Caen, France; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Amnestic mild cognitive impairment (aMCI) is a clinical entity with various potential etiologies including but not limited to Alzheimer's disease. We examined whether a positive ([18F]Florbetapir) beta amyloid positron emission tomography scan, supporting underlying Alzheimer's disease pathophysiology, was associated with specific memory deficits in 48 patients with aMCI (33 beta amyloid positive, 15 beta amyloid negative). Memory was evaluated using an autobiographical fluency task and a word-list learning task with 2 different encoding types (shallow/incidental versus deep/intentional). Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.017DOI Listing
January 2019

Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons.

Neurobiol Aging 2019 Jan 30;77:87-93. Epub 2019 Jan 30.

Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA. Electronic address:

The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.023DOI Listing
January 2019

Prenatal noise stress aggravates cognitive decline and the onset and progression of beta amyloid pathology in a mouse model of Alzheimer's disease.

Neurobiol Aging 2019 Jan 30;77:66-86. Epub 2019 Jan 30.

Department of Neuroscience, Canadian Centre for Behavioural Neuroscience (CCBN), University of Lethbridge, Lethbridge, Alberta, Canada. Electronic address:

Environmental distresses occurring during the sensitive periods of early life may exacerbate the vulnerability to develop physical and mental diseases in old age. Studies have shown the impact of prenatal stress (PS) on the endocrine development and reprogramming of hypothalamic-pituitary-adrenal axis functions in association with cognitive development and susceptibility to neuropsychiatric diseases. Long-term exposure to glucocorticoids can damage the brain and intensify the progression of Alzheimer's disease (AD)-like neuropathological changes, especially in females. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.019DOI Listing
January 2019

Association of amyloid pathology with memory performance and cognitive complaints in cognitively normal older adults: a monozygotic twin study.

Neurobiol Aging 2019 Jan 21;77:58-65. Epub 2019 Jan 21.

Department of Neurology & Alzheimer Center, VU University Medical Center, Neuroscience Amsterdam, Amsterdam, the Netherlands; Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, the Netherlands.

Amyloid pathology in cognitively normal older adults has been associated with low memory performance and cognitive complaints, but findings are conflicting. Using a monozygotic twin design, we further explored this relation. We investigated 199 cognitively normal older adults (96 twin pairs) and assessed cognitive performance, cognitive complaints, and amyloid pathology on positron emission tomography and in the cerebrospinal fluid (CSF). Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.006DOI Listing
January 2019

Associations of amygdala volume and shape with transactive response DNA-binding protein 43 (TDP-43) pathology in a community cohort of older adults.

Neurobiol Aging 2019 Jan 31;77:104-111. Epub 2019 Jan 31.

Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Diagnostic Radiology, Rush University Medical Center, Chicago, IL, USA. Electronic address:

Transactive response DNA-binding protein 43 (TDP-43) pathology is common in old age and is strongly associated with cognitive decline and dementia above and beyond contributions from other neuropathologies. TDP-43 pathology in aging typically originates in the amygdala, a brain region also affected by other age-related neuropathologies such as Alzheimer's pathology. The purpose of this study was two-fold: to determine the independent effects of TDP-43 pathology on the volume, as well as shape, of the amygdala in a community cohort of older adults, and to determine the contribution of amygdala volume to the variance of the rate of cognitive decline after accounting for the contributions of neuropathologies and demographics. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.022DOI Listing
January 2019

Association between circadian rhythms and neurodegenerative diseases.

Lancet Neurol 2019 Mar 12;18(3):307-318. Epub 2019 Feb 12.

Department of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA, USA.

Dysfunction in 24-h circadian rhythms is a common occurrence in ageing adults; however, circadian rhythm disruptions are more severe in people with age-related neurodegenerative diseases, including Alzheimer's disease and related dementias, and Parkinson's disease. Manifestations of circadian rhythm disruptions differ according to the type and severity of neurodegenerative disease and, for some patients, occur before the onset of typical clinical symptoms of neurodegeneration. Evidence from preliminary studies suggest that circadian rhythm disruptions, in addition to being a symptom of neurodegeneration, might also be a potential risk factor for developing Alzheimer's disease and related dementias, and Parkinson's disease, although large, longitudinal studies are needed to confirm this relationship. Read More

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http://dx.doi.org/10.1016/S1474-4422(18)30461-7DOI Listing

Effect of memantine combined with citalopram on cognition of BPSD and moderate Alzheimer's disease: A clinical trial.

Exp Ther Med 2019 Mar 21;17(3):1625-1630. Epub 2018 Dec 21.

Department of Geriatric Psychiatry, Qingdao Mental Health Center, Qingdao, Shandong 266034, P.R. China.

Among Alzheimer's disease (AD) patients, it is very common to develop behavioral and psychological symptoms of dementia (BPSD), which has a close relation to the excess morbidity and mortality, greater healthcare use, earlier institutionalization, and caregiver burden. With evaluation of AD patients, the present study mainly aims to investigate whether citalopram would be efficient for BPSD, and examines citalopram's effects on cognitive function, caregiver distress, safety and tolerability. Eighty patients diagnosed with moderate AD and clinically significant BPSD from April 2015 to January 2016 were enrolled in this study. Read More

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http://dx.doi.org/10.3892/etm.2018.7124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364245PMC

Cysteine-rich granulin-3 rapidly promotes amyloid-β fibrils in both redox states.

Biochem J 2019 Feb 19. Epub 2019 Feb 19.

University of Southern Mississippi, 118 College Dr # 5043, Hattiesburg, Hattiesburg, Mississippi, 39406, United States

Granulins (GRNs 1 - 7) are cysteine-rich proteolytic products of progranulin (PGRN) that have recently been implicated in neurodegenerative diseases including frontotemporal dementia (FTD) and Alzheimer disease (AD). Their precise mechanism in these pathologies remains uncertain, but both inflammatory and lysosomal roles have been observed for GRNs. Among the seven GRNs, GRN‑3 is well-characterized and is implicated within the context of FTD. Read More

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http://dx.doi.org/10.1042/BCJ20180916DOI Listing
February 2019

Hormonal modulation of cholesterol: experimental evidence and possible translational impact.

Expert Rev Endocrinol Metab 2012 May;7(3):309-318

a Department of Clinical Physiopathology, Endocrine Unit, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOThe), University of Florence, Florence, Italy.

Alzheimer's disease (AD) is still an incurable condition. There is in vitro evidence that estrogens exert neuroprotective effects; however, their role in the treatment of AD is still controversial. Approximately 10 years ago, a new gene, named seladin-1 (for selective AD indicator-1), was identified and found to be downregulated in brain regions affected by AD. Read More

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http://dx.doi.org/10.1586/eem.12.12DOI Listing

Misidentification subtype of Alzheimer's disease psychosis predicts a faster cognitive decline.

CPT Pharmacometrics Syst Pharmacol 2019 Feb 19. Epub 2019 Feb 19.

UMR 1137, IAME INSERM, University Paris, Paris, France.

The presence of psychosis is associated with more rapid decline in Alzheimer's disease (AD), but the impact of paranoid (persecutory delusions) and misidentification (misperceptions and/or hallucinations) subtypes of psychosis on the speed of decline in AD is still unclear. Here we analysed data on Alzheimer's Disease Neuroimaging Initiative (ADNI)2 participants with late mild cognitive impairment or AD and we described individual trajectories of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) scores using a semi-mechanistic, logistic model, with a mixed effects based approach, which accounted for drop-out, and adjusted for baseline Mini Mental State Examination scores. The covariate model included psychosis subtypes, age, gender, education, medications and Apo-e ε4 genotype. Read More

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http://dx.doi.org/10.1002/psp4.12389DOI Listing
February 2019

Editorial: Risk Factors and Outcome Predicating Biomarker of Neurodegenerative Diseases.

Front Neurol 2019 4;10:45. Epub 2019 Feb 4.

Institute of Neuroscience, Catholic University of Louvain, Louvain-la-Neuve, Belgium.

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http://dx.doi.org/10.3389/fneur.2019.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369360PMC
February 2019

Targeting TNFR2 as a Novel Therapeutic Strategy for Alzheimer's Disease.

Front Neurosci 2019 4;13:49. Epub 2019 Feb 4.

Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, Faculty of Science and Engineering, University of Groningen, Groningen, Netherlands.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Accumulating experimental evidence shows the important linkage between tumor necrosis factor-α (TNF) and AD, but the exact role of TNF in AD is still not completely understood. Although TNF-inhibitors are successfully used for treating several diseases, total inhibition of TNF can cause side effects, particularly in neurological diseases. Read More

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http://dx.doi.org/10.3389/fnins.2019.00049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369349PMC
February 2019

Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology.

Mol Psychiatry 2019 Feb 18. Epub 2019 Feb 18.

Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Vic, Australia.

Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (β [SE] = 9. Read More

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http://dx.doi.org/10.1038/s41380-019-0375-7DOI Listing
February 2019

Neuropathological and genetic characteristics of a post-mortem series of cases with dementia with Lewy bodies clinically suspected of Creutzfeldt-Jakob's disease.

Parkinsonism Relat Disord 2019 Feb 13. Epub 2019 Feb 13.

Amsterdam UMC, Vrije Universiteit Amsterdam, Dept. of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam, the Netherlands.

Introduction: The disease course of dementia with Lewy bodies (DLB) can be rapidly progressive, clinically resembling Creutzfeldt-Jakob's disease (CJD). To better understand factors contributing to this rapidly progressive disease course, we describe load and distribution of neuropathology, and the presence of possible disease-associated genetic defects in a post-mortem series of DLB cases clinically suspected of CJD.

Methods: We included pathologically confirmed DLB cases with a disease duration of 3. Read More

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http://dx.doi.org/10.1016/j.parkreldis.2019.02.011DOI Listing
February 2019

Hospitalization, surgery, and incident dementia.

Alzheimers Dement 2019 Feb 15. Epub 2019 Feb 15.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychology, University of Southern California, Los Angeles, CA, USA. Electronic address:

Introduction: We evaluated whether hospitalization with or without surgery increases risk for dementia or Alzheimer's disease.

Methods: A clinical sample (843 clinically diagnosed dementia cases; 1686 matched nondemented individuals) was identified from Swedish Twin Registry studies. A register-based sample (4293 cases; 21,465 matched controls) was identified by linkage of Swedish Twin Registry to Swedish Patient Registry records. Read More

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http://dx.doi.org/10.1016/j.jalz.2018.12.005DOI Listing
February 2019

Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer's disease.

J Neuroinflammation 2019 Feb 18;16(1):44. Epub 2019 Feb 18.

Neurology Department, Fondazione Istituto Giuseppe Giglio, Cefalù, PA, Italy.

Background: Aβ peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNβ1a in attenuating cognitive impairment and inflammation in an animal model of AD. Read More

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http://dx.doi.org/10.1186/s12974-019-1417-4DOI Listing
February 2019

Impaired behavioural flexibility related to white matter microgliosis in the TgAPP21 rat model of Alzheimer disease.

Brain Behav Immun 2019 Feb 15. Epub 2019 Feb 15.

Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, Western University, London ON, Canada; Department of Clinical Neurological Sciences, University Hospital, Western University, London, ON, Canada. Electronic address:

Executive dysfunction and white matter inflammation continue to be relatively understudied in rodent models of Alzheimer's disease (AD). Behavioural inflexibility is an important component of executive dysfunction that can be further categorized as perseverative or regressive, which respectively specify whether maladaptive persistence occurs early or late during a behavioural change. Previous studies of the TgAPP21 rat model of AD (expressing pathogenic hAPP) suggested a potentially spontaneous increase of regressive behavioral inflexibility. Read More

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http://dx.doi.org/10.1016/j.bbi.2019.02.013DOI Listing
February 2019

Early Awareness of Alzheimer Disease: A Neurologist's Personal Perspective.

Authors:
Daniel M Gibbs

JAMA Neurol 2019 Feb 18. Epub 2019 Feb 18.

Portland, Oregon.

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http://dx.doi.org/10.1001/jamaneurol.2018.4910DOI Listing
February 2019

Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease.

J Alzheimers Dis 2019 Feb 13. Epub 2019 Feb 13.

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child health (DINOGMI), University of Genoa, Italy.

Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET.

Objective: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e. Read More

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http://dx.doi.org/10.3233/JAD-181022DOI Listing
February 2019
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The Clinical Phenotype of Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

J Alzheimers Dis 2019 Feb 8. Epub 2019 Feb 8.

Department of Neurology, Brain Center Rudolph Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: Type 2 diabetes mellitus (T2DM) increases the risk of vascular cognitive impairment (VCI). It is unknown which type of vascular lesions and co-morbid etiologies, in particular Alzheimer's disease pathology, are associated with T2DM in patients with VCI, and how this relates to cognition and prognosis.

Objective: To compare brain MRI and cerebrospinal fluid (CSF) markers, cognition, and prognosis in patients with possible VCI with and without T2DM. Read More

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http://dx.doi.org/10.3233/JAD-180914DOI Listing
February 2019

Neurosteroids and oxysterols as potential therapeutic agents for glaucoma and Alzheimer's disease.

Neuropsychiatry (London) 2018 ;8(1):344-359

Taylor Family Institute for Innovative Psychiatric Research, Akita University Graduate School of Medicine, Akita, Japan.

Glaucoma is one of the most frequent causes of visual impairment worldwide and involves selective damage to retinal ganglion cells (RGCs) resulting in degeneration of neural pathways connecting retina to visual cortex. It is of interest that similarities in pathological changes have been described in Alzheimer's disease (AD), the most common cause of progressive memory loss and dementia in older people. Accumulation of amyloid-beta (Abeta) and hyperphosphorylated tau is thought to contribute to apoptotic neuronal death in Alzheimer's disease, and similar changes have been linked to apoptotic RGC death in glaucoma. Read More

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http://dx.doi.org/10.4172/Neuropsychiatry.1000356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377075PMC
January 2018

Effect of superparamagnetic nanoparticles coated with various electric charges on α-synuclein and β-amyloid proteins fibrillation process.

Int J Nanomedicine 2019 23;14:799-808. Epub 2019 Jan 23.

National Institute of Genetic Engineering and Biotechnology, Tehran, Iran,

Background: Most of nanoparticles are nontoxic and have high absorption capability. Therefore, nanoparticles binding can effectively restrain fibrillation of β-amyloid and α-synuclein proteins and eventually prevent the toxicity of pathogenesis peptide of Alzheimer. Super paramagnetic iron oxide nanoparticles (SPIONs) contain iron oxide core which can be connected to a special part through magnetic coating. Read More

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http://dx.doi.org/10.2147/IJN.S190354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361412PMC
January 2019

[The purinergic receptor P2X7, a new therapeutic target in Alzheimer' disease].

Med Sci (Paris) 2019 Feb 18;35(2):97-99. Epub 2019 Feb 18.

Sorbonne Université, Inserm, CNRS, Institut de la Vision, 17, rue Moreau, 75012 Paris, France.

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http://dx.doi.org/10.1051/medsci/2019017DOI Listing
February 2019

Staging biomarkers in preclinical autosomal dominant Alzheimer's disease by estimated years to symptom onset.

Alzheimers Dement 2019 Feb 14. Epub 2019 Feb 14.

Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address:

Introduction: Staging preclinical Alzheimer disease (AD) by the expected years to symptom onset (EYO) in autosomal dominant AD (ADAD) through biomarker correlations is important.

Methods: We estimated the correlation matrix between EYO/cognition and imaging/CSF biomarkers, and searched for the EYO cutoff where a change in the correlations occurred before and after the cutoff among the asymptomatic mutation carriers of ADAD. We then estimated the longitudinal rate of change for biomarkers/cognition within each preclinical stage defined by the EYO. Read More

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http://dx.doi.org/10.1016/j.jalz.2018.12.008DOI Listing
February 2019

Dulaglutide ameliorates STZ induced AD-like impairment of learning and memory ability by modulating hyperphosphorylation of tau and NFs through GSK3β.

Biochem Biophys Res Commun 2019 Feb 14. Epub 2019 Feb 14.

Pathophysiology Department, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Electronic address:

Dulaglutide, a novel long-acting glucagon-like peptide 1 (GLP-1) receptor agonist, is an incretin mimetic approved for type 2 diabetes mellitus (T2DM) treatment. Alzheimer's disease (AD) is called type 3 diabetes. The aim of this study is to explore the effects of dulaglutide on the learning and memory impairment in AD mice induced by injection of streptozocin (STZ) via intracerebroventricularly (i. Read More

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http://dx.doi.org/10.1016/j.bbrc.2019.01.103DOI Listing
February 2019
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Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults.

Neurobiol Aging 2019 Jan 24;77:13-19. Epub 2019 Jan 24.

Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.

Age-related cognitive decline is a public health problem but highly diverse and difficult to predict. We captured nonoverlapping cognitive phenotypes in high-functioning adults and identified baseline factors differentiating trajectories. Three hundred fourteen functionally normal adults (M = 69 y) completed 2+ visits. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.01.007DOI Listing
January 2019
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Synthesis and evaluation of novel GSK-3β inhibitors as multifunctional agents against Alzheimer's disease.

Eur J Med Chem 2019 Feb 8;167:211-225. Epub 2019 Feb 8.

Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China. Electronic address:

To target the multi-facets of Alzheimer's disease (AD), a series of novel GSK-3β inhibitors containing the 2,3-diaminopyridine moiety were designed and synthesized. The amide derivatives 5a-f showed moderate potency against GSK-3β with weak Cu, Zn and Al chelating ability. The imine derivatives 9a, 9b and 9e were potent GSK-3β inhibitors and selective Cuand Al chelators. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.02.001DOI Listing
February 2019

GeneMatch: A novel recruitment registry using at-home APOE genotyping to enhance referrals to Alzheimer's prevention studies.

Alzheimers Dement 2019 Feb 6. Epub 2019 Feb 6.

Banner Alzheimer's Institute, Phoenix, AZ, USA.

Introduction: Recruitment for Alzheimer's disease (AD) prevention research studies is challenging because of lack of awareness among cognitively healthy adults coupled with the high screen fail rate due to participants not having a genetic risk factor or biomarker evidence of the disease. Participant recruitment registries offer one solution for efficiently and effectively identifying, characterizing, and connecting potential eligible volunteers to studies.

Methods: Individuals aged 55-75 years who live in the United States and self-report not having a diagnosis of cognitive impairment such as MCI or dementia are eligible to join GeneMatch. Read More

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http://dx.doi.org/10.1016/j.jalz.2018.12.007DOI Listing
February 2019
1 Read

Continuing pharmacy education practices in geriatric care among pharmacists in the Upper Midwest.

J Am Pharm Assoc (2003) 2019 Feb 13. Epub 2019 Feb 13.

Objectives: To summarize select continuing pharmacy education (CPE) topics and hours related to geriatric care completed by community, hospital/clinic, and long-term care (LTC)/consultant pharmacists in the previous 12 months, whether pharmacy workplace influenced topic selection or completion, and to describe CPE sources used by community versus hospital/clinic pharmacists.

Design: Cross-sectional survey (2017).

Setting And Participants: Licensed pharmacists in North Dakota, South Dakota, Minnesota, Iowa, and Nebraska with primary practice settings in community pharmacies, hospitals, or clinics or those practicing as consultant pharmacists. Read More

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http://dx.doi.org/10.1016/j.japh.2018.12.020DOI Listing
February 2019
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Laser ablation ICP-MS for simultaneous quantitative imaging of iron and ferroportin in hippocampus of human brain tissues with Alzheimer's disease.

Talanta 2019 May 15;197:413-421. Epub 2019 Jan 15.

Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Julian Claveria 8, 33006 Oviedo, Spain.

Laser ablation inductively coupled plasma - mass spectrometry (LA-ICP-MS) is proposed for a better understanding of metals and proteins distribution in micrometre structures of human brain tissues. Simultaneous absolute quantitative imaging of Fe and ferroportin (FPN), in 5 µm thick tissue sections of the stratum pyramidale of hippocampus CA1 region, was carried out for Alzheimer disease (AD) patients and healthy controls (HC). For the imaging of FPN by LA-ICP-MS, antibodies were labelled via carbodiimide crosslinking with fluorescent gold nanoclusters (AuNCs) of 2. Read More

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http://dx.doi.org/10.1016/j.talanta.2019.01.056DOI Listing
May 2019
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Tackling neuroinflammation and cholinergic deficit in Alzheimer's disease: Multi-target inhibitors of cholinesterases, cyclooxygenase-2 and 15-lipoxygenase.

Eur J Med Chem 2019 Feb 8;167:161-186. Epub 2019 Feb 8.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt. Electronic address:

Neuroinflammation and cholinergic deficit are key detrimental processes involved in Alzheimer's disease. Hence, in the search for novel and effective treatment strategies, the multi-target-directed ligand paradigm was applied to the rational design of two series of new hybrids endowed with anti-inflammatory and anticholinesterase activity via triple targeting properties, namely able to simultaneously hit cholinesterases, cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX) enzymes. Among the synthesized compounds, triazoles 5b and 5d, and thiosemicarbazide hybrid 6e emerged as promising new hits, being able to effectively inhibit human butyrylcholinesterase (hBChE), COX-2 and 15-LOX enzymes with a higher inhibitory potency than the reference inhibitors tacrine (for hBChE inhibition), celecoxib (for COX-2 inhibition) and both NDGA and Zileuton (for 15-LOX inhibition). Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.02.012DOI Listing
February 2019
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Synthesis and evaluation of tetrahydroisoquinoline-benzimidazole hybrids as multifunctional agents for the treatment of Alzheimer's disease.

Eur J Med Chem 2019 Feb 4;167:133-145. Epub 2019 Feb 4.

Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China. Electronic address:

A novel series of tetrahydroisoquinoline-benzimidazole hybrids have been designed and synthesized as multifunctional agents against Alzheimer's disease (AD). These compounds were evaluated for their inhibition of neuroinflammation and human β-secretase (hBACE1), and neuroprotective activity. Among them, compound BD3 possessed significant anti-neuroinflammatory activity (IC = 5. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.02.008DOI Listing
February 2019

Dual Effect of Doxazosin: Anticancer Activity on SH-SY5Y Neuroblastoma Cells and Neuroprotection on an In Vitro Model of Alzheimer's Disease.

Neuroscience 2019 Feb 13. Epub 2019 Feb 13.

Programa de Pós-Graduação em Ciências Biológicas-Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Several studies have demonstrated the antitumor effect of doxazosin, an α1-adrenergic blocker, against glioma and breast, bladder and prostate cancers. Doxazosin is also being evaluated as a treatment for posttraumatic stress disorder and alcoholism, and α1-adrenergic blockers have been linked to neuroprotection in neurodegenerative disorders, such as Alzheimer's Disease (AD). Cancer and AD have an inverse relationship in many aspects, with several factors that contribute to apoptosis inhibition and proliferation being increased in cancers but decreased in AD. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2019.02.005DOI Listing
February 2019
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Complement C3a receptor antagonist attenuates tau hyperphosphorylation via glycogen synthase kinase 3β signaling pathways.

Eur J Pharmacol 2019 Feb 13. Epub 2019 Feb 13.

Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Neurofibrillary tangles aggregated from hyperphosphorylated tau protein are the main pathological feature of Alzheimer's disease (AD). Complement C3 (or C3a) is the core component of the complement system and is associated with AD pathological processes. However, it remains unclear whether C3a or the C3a receptor has any effect on tau phosphorylation. Read More

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http://dx.doi.org/10.1016/j.ejphar.2019.02.020DOI Listing
February 2019

Aegle marmelos leaf extract ameliorates the cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin in male rats.

Life Sci 2019 Feb 13. Epub 2019 Feb 13.

Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Sector-125, Noida 201313, India. Electronic address:

Aims: Aegle marmelos (L.) Correa (A. marmelos) has been used in Ayurvedic medicine as a brain tonic however its neuroprotective effect against streptozotocin (STZ) induced cognitive impairment and oxidative stress has not been reported yet in vivo. Read More

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http://dx.doi.org/10.1016/j.lfs.2019.02.032DOI Listing
February 2019
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Artificial intelligence in neuropathology: deep learning-based assessment of tauopathy.

Lab Invest 2019 Feb 15. Epub 2019 Feb 15.

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Accumulation of abnormal tau in neurofibrillary tangles (NFT) occurs in Alzheimer disease (AD) and a spectrum of tauopathies. These tauopathies have diverse and overlapping morphological phenotypes that obscure classification and quantitative assessments. Recently, powerful machine learning-based approaches have emerged, allowing the recognition and quantification of pathological changes from digital images. Read More

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http://dx.doi.org/10.1038/s41374-019-0202-4DOI Listing
February 2019
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Repeated cold exposures protect a mouse model of Alzheimer's disease against cold-induced tau phosphorylation.

Mol Metab 2019 Jan 26. Epub 2019 Jan 26.

Faculty of Pharmacy, Université Laval, Quebec City, Qc, Canada; Neurosciences Axis, CHU de Québec-Université Laval Research Center, Quebec City, Qc, Canada. Electronic address:

Objective: Old age is associated with a rise in the incidence of Alzheimer's disease (AD) but also with thermoregulatory deficits. Indicative of a link between the two, hypothermia induces tau hyperphosphorylation. The 3xTg-AD mouse model not only develops tau and amyloid pathologies in the brain but also metabolic and thermoregulatory deficits. Read More

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http://dx.doi.org/10.1016/j.molmet.2019.01.008DOI Listing
January 2019
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Delusions in Alzheimer Disease: What Researchers Should Not Forget.

Am J Geriatr Psychiatry 2019 Jan 9. Epub 2019 Jan 9.

Department of Psychiatry (KP), University of Pittsburgh School of Medicine, Pittsburgh. Electronic address:

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http://dx.doi.org/10.1016/j.jagp.2018.12.034DOI Listing
January 2019
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Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway.

Life Sci 2019 Feb 12. Epub 2019 Feb 12.

Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China. Electronic address:

Aims: Edaravone potentially alleviates cognitive deficits in a mouse model of Alzheimer's disease (AD). However, the mechanism of edaravone in suppressing AD progression remains unclear. We aim to investigate the mechanism of edaravone in suppressing oxidative stress-mediated AD progression in vitro. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00243205193011
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http://dx.doi.org/10.1016/j.lfs.2019.02.025DOI Listing
February 2019
3 Reads
2.702 Impact Factor

Melatonin protective effect against amyloid β-induced neurotoxicity mediated by mitochondrial biogenesis; involvement of hippocampal Sirtuin-1 signaling pathway.

Physiol Behav 2019 Feb 12;204:65-75. Epub 2019 Feb 12.

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

Melatonin has a potential therapeutic value in Alzheimer's disease (AD), a disease that is associated with a dramatic decline in memory and cognitive abilities. The aggregation of the amyloid β (Aβ) peptide, a hallmark of AD, deactivates mitochondrial biogenesis and antioxidant defenses. Melatonin as an endogenous antioxidant, decreases in plasma and cerebrospinal fluid of AD patients. Read More

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http://dx.doi.org/10.1016/j.physbeh.2019.02.016DOI Listing
February 2019
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A walk through tau therapeutic strategies.

Acta Neuropathol Commun 2019 Feb 15;7(1):22. Epub 2019 Feb 15.

AXON Neuroscience R&D Services SE, Dvorakovo nabrezie 10, 811 02, Bratislava, Slovakia.

Tau neuronal and glial pathologies drive the clinical presentation of Alzheimer's disease and related human tauopathies. There is a growing body of evidence indicating that pathological tau species can travel from cell to cell and spread the pathology through the brain. Throughout the last decade, physiological and pathological tau have become attractive targets for AD therapies. Read More

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https://actaneurocomms.biomedcentral.com/articles/10.1186/s4
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http://dx.doi.org/10.1186/s40478-019-0664-zDOI Listing
February 2019
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SET SUMOylation promotes its cytoplasmic retention and induces tau pathology and cognitive impairments.

Acta Neuropathol Commun 2019 Feb 15;7(1):21. Epub 2019 Feb 15.

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

PP2A is a major regulator of tau phosphorylation, which is principally regulated by an endogenous nuclear protein inhibitor 2 of PP2A (I), also named SET. However, how SET is post-translationally regulated and translocates from the nucleus to the cytoplasm remain incompletely understood. Here we show SET is SUMOylated at K68 residue that induces its cytoplasmic retention, resulting in Alzheimer disease (AD) like tau pathology and cognitive defects. Read More

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http://dx.doi.org/10.1186/s40478-019-0663-0DOI Listing
February 2019
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Atrial Fibrillation and Risk of Dementia: Epidemiology, Mechanisms, and Effect of Anticoagulation.

Front Neurosci 2019 31;13:18. Epub 2019 Jan 31.

Department of Clinical Research, Federal University of Uberlandia, Uberlândia, Brazil.

Atrial fibrillation (AF) is one of the cardiovascular risk factors for dementia. Several longitudinal studies have reported an association between AF and dementia independently of stroke history. Although the mechanisms underlying this association are not fully understood, proposed mechanisms include cerebral hypoperfusion, inflammation, genetic factors, cerebral microbleeds, and recurrent silent cerebral ischemia. Read More

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http://dx.doi.org/10.3389/fnins.2019.00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365433PMC
January 2019
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Highly potent and selective aryl-1,2,3-triazolyl benzylpiperidine inhibitors toward butyrylcholinesterase in Alzheimer's disease.

Bioorg Med Chem 2018 Dec 23. Epub 2018 Dec 23.

School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Café s/n, 14040-930 Ribeirão Preto, SP, Brazil. Electronic address:

Acetylcholinesterase (AChE) is the key enzyme targeted in Alzheimer's disease (AD) therapy, nevertheless butyrylcholinesterase (BuChE) has been drawing attention due to its role in the disease progression. Thus, we aimed to synthesize novel cholinesterases inhibitors considering structural differences in their peripheral site, exploiting a moiety replacement approach based on the potent and selective hAChE drug donepezil. Hence, two small series of N-benzylpiperidine based compounds have successfully been synthesized as novel potent and selective hBuChE inhibitors. Read More

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http://dx.doi.org/10.1016/j.bmc.2018.12.030DOI Listing
December 2018
1 Read