116,812 results match your criteria Alzheimer Disease

Dual-target compounds for Alzheimer's disease: Natural and synthetic AChE and BACE-1 dual-inhibitors and their structure-activity relationship (SAR).

Eur J Med Chem 2021 Apr 24;221:113492. Epub 2021 Apr 24.

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal. Electronic address:

Alzheimer's disease (AD) is a chronic neurodegenerative disease and represents the major cause of dementia worldwide. Currently, there are no available treatments capable to deliver disease-modifying effects, and the available drugs can only alleviate the symptoms. The exact pathology of AD is not yet fully understood and several hallmarks such as the presence of amyloid-β (Aβ) senile plaques, neurofibrillary tangles (NFTs) as well as the loss of cholinergic function have been associated to AD. Read More

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Huprine Y - tryptophan heterodimers with potential implication to Alzheimer's disease treatment.

Bioorg Med Chem Lett 2021 May 10:128100. Epub 2021 May 10.

Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic; Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. Electronic address:

The search for novel and effective therapeutics for Alzheimer's disease (AD) is the main quest that remains to be resolved. The goal is to find a disease-modifying agent able to confront the multifactorial nature of the disease positively. Herewith, a family of huprineY-tryptophan heterodimers was prepared, resulting in inhibition of cholinesterase and neuronal nitric oxide synthase enzymes, with effect against amyloid-beta (Aβ) and potential ability to cross the blood-brain barrier. Read More

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Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

Introduction: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment.

Methods: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ) /Aβ and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4.

Results: We observed a significant CSF Aβ /Aβ × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. Read More

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Longitudinal CSF proteomics identifies NPTX2 as a prognostic biomarker of Alzheimer's disease.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

National Institute of Mental Health, Bethesda, Maryland, USA.

Introduction: Biomarkers that reflect pathologic processes affecting neuronal function during preclinical and early stages of Alzheimer's disease (AD) are needed to aid drug development.

Methods: A targeted, stable isotope, quantitative mass spectrometry-based investigation of longitudinal changes in concentrations of previously identified candidate biomarkers was performed in cerebrospinal fluid (CSF) of Alzheimer's Disease Neuroimaging Initiative participants who were classified as cognitively normal (CN; n = 76) or with mild cognitive impairment (MCI; n = 111) at baseline.

Results: Of the candidate biomarkers, the CSF concentration of neuronal pentraxin 2 (NPTX2), a protein involved in synaptic function, exhibited rates of change that were significantly different between three comparison groups (i. Read More

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Health utility in preclinical and prodromal Alzheimer's disease for establishing the value of new disease-modifying treatments-EQ-5D data from the Swedish BioFINDER study.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

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

Quality of life and health utility are important outcomes for patients with Alzheimer's disease (AD) and central for demonstrating the value of new treatments. Estimates in biomarker-confirmed AD populations are missing, potentially delaying payer approval of treatment. We examined whether health utility, assessed with the EuroQoL-5 3-level version (EQ-5D-3L), differed between individuals with a positive or negative amyloid beta (Aβ) biomarker in patients with mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants from the Swedish BioFINDER study (n = 578). Read More

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Knowledge gaps in Alzheimer's disease immune biomarker research.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Division of Epidemiology, Department of Health Sciences Research, Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.

Considerable evidence has accumulated implicating a role for immune mechanisms in moderating the pathology in Alzheimer's disease dementia. However, the appropriate therapeutic target, the appropriate direction of manipulation, and the stage of disease at which to begin treatment remain unanswered questions. Part of the challenge derives from the absence of any selective pressure to develop a coordinated beneficial immune response to severe neural injury in adults. Read More

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Towards clinical application of tau PET tracers for diagnosing dementia due to Alzheimer's disease.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Lund University, Clinical Memory Research Unit, Lund, Sweden.

The recent development of several tau positron emission tomography (PET) tracers represents a major milestone for the Alzheimer's disease (AD) field. These tau PET tracers bind tau neurofibrillary tangles, a key neuropathological characteristic of AD that is tightly linked to synaptic loss, brain atrophy, and cognitive decline. It is notable that these tau PET tracers show low uptake in most non-AD tauopathies and other neurodegenerative disorders, resulting in a diagnostic specificity that is superior to that of amyloid beta (Aβ) PET and biofluid markers, especially at an older age when incidental Aβ pathology is common. Read More

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Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Department of Medicine and Surgery, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.

Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.

Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U. Read More

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Validation of The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in behavioural variant Frontotemporal Dementia and Alzheimer's Disease.

Int J Geriatr Psychiatry 2021 May 13. Epub 2021 May 13.

Human Cognitive Neuroscience -Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh.

The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was developed to assess cognitive and behavioural changes in an anterior frontotemporal syndrome (executive functions, language, fluency and behaviour), common in Amyotrophic Lateral Sclerosis (ALS) and also assesses posterior cerebral dysfunction (memory and visuospatial abilities).

Objectives: To validate the ECAS in behavioural variant Frontotemporal Dementia (bvFTD) without ALS, as compared with Alzheimer's Disease (AD), against comprehensive neuropsychological assessment. Compare its sensitivity to that of the Addenbrooke's Cognitive Examination (ACE-III) and investigate behavioural changes in both types of dementia. Read More

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An insight into the role of Artificial Intelligence in the early diagnosis of Alzheimer's disease.

CNS Neurol Disord Drug Targets 2021 May 11. Epub 2021 May 11.

Department of Pharmaceutical Medicine, School of Pharmaceutical Education and Research, Jamia Humdard, New Delhi India Pharmacology, India.

Background: The complication of Alzheimer's disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the foremost hurdle behind its treatment. Read More

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Multi-Target-Directed Ligands as an Effective Strategy for the Treatment of Alzheimer's Disease.

Curr Med Chem 2021 May 11. Epub 2021 May 11.

Department of Chemistry, Central University of Punjab, Bathinda, Punjab-151001, India.

Alzheimer's disease (AD) is a complex neurological disorder, and multiple pathological factors are believed to be involved in the genesis and progression of the disease. A number of hypotheses, including Acetylcholinesterase, Monoamine oxidase, β-Amyloid, Tau protein, etc., have been proposed for the initiation and progression of the disease. Read More

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Surface Foliation Based Brain Morphometry Analysis.

Multimodal Brain Image Anal Math Found Comput Anat (2019) 2019 10;11846:186-195. Epub 2019 Oct 10.

Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.

Brain morphometry plays a fundamental role in neuroimaging research. In this work, we propose a novel method for brain surface morphometry analysis based on surface foliation theory. Given brain cortical surfaces with automatically extracted landmark curves, we first construct finite foliations on surfaces. Read More

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October 2019

From the low-density lipoprotein receptor-related protein 1 to neuropathic pain: a potentially novel target.

Pain Rep 2021 9;6(1):e898. Epub 2021 Mar 9.

Department of Neurology, University Hospital of Würzburg, Würzburg, Germany.

This review describes the roles of the low-density lipoprotein receptor-related protein 1 (LRP-1) in inflammatory pathways, nerve nerve degeneration and -regeneration and in neuropathic pain. Induction of LRP-1 is able to reduce the activation of the proinflammatory NFκB-mediated pathway and the mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase and p38 signaling pathways, in turn decreasing the production of inflammatory mediators. Low-density lipoprotein receptor-related protein 1 activation also decreases reactive astrogliosis and polarizes microglial cells and macrophages from a proinflammatory phenotype (M1) to an anti-inflammatory phenotype (M2), attenuating the neuroinflammatory environment. Read More

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Aberrant expression of miR-148a-3p in Alzheimer's disease and its protective role against amyloid-β induced neurotoxicity.

Neurosci Lett 2021 May 9:135953. Epub 2021 May 9.

Department of Neurology, Shanxian Central Hospital, Heze 274300, Shandong, China. Electronic address:

Objective: The current study investigated the expression change and clinical value of miR-148a-3p in AD patients, and further examined the role of miR-148a-3p in Aβ-induced neurotoxicity in SH-SY5Y cells.

Material And Methods: qRT-PCR was used for the measurement of miR-148a-3p expression levels. ROC curve was established to calculate the diagnostic value of serum miR-148a-3p for AD. Read More

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VEGF counteracts amyloid-β-induced synaptic dysfunction.

Cell Rep 2021 May;35(6):109121

Institut NeuroMyoGène (INMG), Synaptopathies and Autoantibodies, Institut National de la Santé et de la Recherche Médicale (INSERM), U1217, Centre National de la Recherche Scientifique (CNRS) UMR5310, 69000 Lyon, France; Université Claude Bernard Lyon 1, 69000 Lyon, France. Electronic address:

The vascular endothelial growth factor (VEGF) pathway regulates key processes in synapse function, which are disrupted in early stages of Alzheimer's disease (AD) by toxic-soluble amyloid-beta oligomers (Aβo). Here, we show that VEGF accumulates in and around Aβ plaques in postmortem brains of patients with AD and in APP/PS1 mice, an AD mouse model. We uncover specific binding domains involved in direct interaction between Aβo and VEGF and reveal that this interaction jeopardizes VEGFR2 activation in neurons. Read More

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Beyond the : "Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease Results From 2 Phase III Clinical Trials".

AJR Am J Roentgenol 2021 May 12. Epub 2021 May 12.

Department of Medicine, Alzheimer's Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, William S. Middleton Memorial Veterans Hospital.

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Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum.

Hum Brain Mapp 2021 May 12. Epub 2021 May 12.

Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

The structural covariance network (SCN) has provided a perspective on the large-scale brain organization impairment in the Alzheimer's Disease (AD) continuum. However, the successive structural impairment across brain regions, which may underlie the disrupted SCN in the AD continuum, is not well understood. In the current study, we enrolled 446 subjects with AD, mild cognitive impairment (MCI) or normal aging (NA) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Read More

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Hesperetin ameliorates hepatic oxidative stress and inflammation the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD.

Food Funct 2021 May;12(9):3898-3918

Institute of Biomedical Research, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, China.

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease. Dietary supplementation has become a promising strategy for managing NAFLD. Hesperetin, a citrus flavonoid, is mainly found in citrus fruits (oranges, grapefruit, and lemons) and possesses multiple pharmacological properties, including anti-cancer, anti-Alzheimer and anti-diabetic effects. Read More

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Frailty is Associated With Frontal Cortex-Related Cognitive Function in Patients With Alzheimer Disease.

J Geriatr Psychiatry Neurol 2021 May 12:8919887211016062. Epub 2021 May 12.

Department of Neuropsychiatry, 59082Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Ling-Ya District, Kaohsiung.

Objective: We compared the cognitive functions of Alzheimer disease (AD) patients who were robust, frail or pre-frail and hypothesized that declines in frontal cortex-related neuropsychological function would be associated with frailty.

Method: One hundred and sixty outpatients aged 65 years or older with mild AD were enrolled. Cognitive function was assessed using the Cognitive Ability Screening Instrument and further classified into 4 clusters (recent memory, frontal cortex cluster, posterior cortex cluster, and orientation). Read More

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Apelin-13 protects human neuroblastoma SH-SY5Y cells against amyloid-beta induced neurotoxicity: Involvement of anti oxidant and anti apoptotic properties.

J Basic Clin Physiol Pharmacol 2021 May 10. Epub 2021 May 10.

Golestan Neuroscience Research Center (GNRC), Department of Anatomy, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

Objectives: We investigated the effect of apelin-13 on the cellular model of AD, amyloid-β (Aβ) treated SH-SY5Y cells in rats.

Methods: The SH-SY5Y cells were pretreated with different doses of apelin-13 (1, 2.5, 5, and 10 μg/mL), half an hour before adding 50% Aβ treatment. Read More

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Activating transcription factor 4-dependent lactate dehydrogenase activation as a protective response to amyloid beta toxicity.

Brain Commun 2021 26;3(2):fcab053. Epub 2021 Mar 26.

Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK.

Accumulation of amyloid beta peptides is thought to initiate the pathogenesis of Alzheimer's disease. However, the precise mechanisms mediating their neurotoxicity are unclear. Our microarray analyses show that, in models of amyloid beta 42 toxicity, genes involved in the unfolded protein response and metabolic processes are upregulated in brain. Read More

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Upregulated expression of a subset of genes in ;/ mice: Evidence of an interaction between diabetes-linked obesity and Alzheimer's disease.

FASEB Bioadv 2021 May 2;3(5):323-333. Epub 2021 Mar 2.

Department of Aging Neurobiology Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology Obu Aichi Japan.

Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at molecular levels, we performed gene expression analysis of ;/ mice, which were generated by crossing transgenic AD model mice (APP23 mice) with / mice, which are obese and mildly diabetic. Read More

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The contact activation system and vascular factors as alternative targets for Alzheimer's disease therapy.

Res Pract Thromb Haemost 2021 May 3;5(4):e12504. Epub 2021 May 3.

Patricia and John Rosenwald Laboratory of Neurobiology and Genetics The Rockefeller University New York NY USA.

Alzheimer's disease (AD) is the most common neurodegenerative disease, affecting millions of people worldwide. Extracellular beta-amyloid (Aβ) plaques and neurofibrillary tau tangles are classical hallmarks of AD pathology and thus are the prime targets for AD therapeutics. However, approaches to slow or stop AD progression and dementia by reducing Aβ production, neutralizing toxic Aβ aggregates, or inhibiting tau aggregation have been largely unsuccessful in clinical trials. Read More

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Detection of retinal and blood Aβ oligomers with nanobodies.

Alzheimers Dement (Amst) 2021 6;13(1):e12193. Epub 2021 May 6.

School of Medicine Western Sydney University Campbelltown New South Wales Australia.

Introduction: Abnormal retinal changes are increasingly recognized as an early pathological change in Alzheimer's disease (AD). Although amyloid beta oligomers (Aβo) have been shown to accumulate in the blood and retina of AD patients and animals, it is not known whether the early Aβo deposition precedes their accumulation in brain.

Methods And Results: Using nanobodies targeting Aβ and Aβ oligomers we were able to detect Aβ oligomers in the retina and blood but not in the brain of 3-month-old APP/PS1 mice. Read More

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Risk Factors for Falls in Patients with Alzheimer Disease: A Retrospective Study of Balance, Cognition, and Visuospatial Ability.

Dement Geriatr Cogn Dis Extra 2021 Jan-Apr;11(1):58-63. Epub 2021 Mar 22.

Department of Occupational Therapy, Kyorin University, Mitaka, Japan.

Aim: This study aimed to determine the main risk factors for falls in patients with Alzheimer disease (AD) by comparing balance, cognition, and visuospatial ability between those who have experienced a fall and those who have not.

Methods: Forty-seven AD patients were admitted to a ward for patients with dementia (22 men and 25 women). The balance of patients was evaluated using the Functional Reach Test (FRT), the one-leg standing duration, and the Timed Up and Go (TUG) test. Read More

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Psychometric Properties of the Persian Montreal Cognitive Assessment in Mild Cognitive Impairment and Alzheimer Disease.

Dement Geriatr Cogn Dis Extra 2021 Jan-Apr;11(1):51-57. Epub 2021 Mar 19.

Linnaeus Centre HEAD, Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.

Introduction: The Montreal Cognitive Assessment (MoCA) is a cognitive screening test widely used in clinical practice and suited for the detection of Mild Cognitive Impairment (MCI). The aims were to evaluate the psychometric properties of the Persian MoCA as a screening test for mild cognitive dysfunction in Iranian older adults and to assess its accuracy as a screening test for MCI and mild Alzheimer disease (AD).

Method: One hundred twenty elderly with a mean age of 73. Read More

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Lactoferrin in cerebrospinal fluid and saliva is not a diagnostic biomarker for Alzheimer's disease in a mixed memory clinic population.

EBioMedicine 2021 May 7;67:103361. Epub 2021 May 7.

Department of Neurology, Danish Dementia Research Centre (DDRC), Copenhagen University Hospital, Rigshospitalet, Denmark.

Background: The pathological changes in Alzheimer's Disease (AD) and other neurodegenerative disorders begin decades prior to their clinical expression. However, the clinical diagnosis of neurodegenerative dementias is not straightforward. Lactoferrin is an iron-binding, antimicrobial glycoprotein with a plethora of functions, including acting as an important immune modulator and by having a bacteriocidic effect. Read More

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JWX-A0108, a positive allosteric modulator of α7 nAChR, attenuates cognitive deficits in APP/PS1 mice by suppressing NF-κB-mediated inflammation.

Int Immunopharmacol 2021 May 8;96:107726. Epub 2021 May 8.

Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao 266000, China. Electronic address:

Neuroinflammation plays an early and prominent role in the pathology of Alzheimer's disease (AD). Studies have shown that cholinergic lesion is a contributor for the pathophysiology of AD. The α7 nicotinic acetylcholine receptors (nAChRs), a subtype of nAChRs, are abundantly expressed in the brain regions related to cognition and memory, such as hippocampus and frontal cortex. Read More

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Shenqi Yizhi Granule attenuates Aβ induced cognitive dysfunction via inhibiting JAK2/STAT3 activated astrocyte reactivity.

Exp Gerontol 2021 May 8:111400. Epub 2021 May 8.

Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China. Electronic address:

Shenqi Yizhi Granule (SYG), a modern preparation herbs based on the theory of traditional Chinese medicine, has been proved to be effective against Alzheimer's disease in clinical trials, APP/PS1 mice and 5XFAD transgenic mice. But the underlying mechanism remains ambiguous. Increasing evidence supports the crucial role of astrocyte reactivity in the pathogenesis of Alzheimer's disease (AD). Read More

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