109,765 results match your criteria Alzheimer Disease & Associated Disorders[Journal]


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

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

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

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

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

Altered phobic reactions in frontotemporal dementia: A behavioural and neuroanatomical analysis.

Cortex 2020 Jun 14;130:100-110. Epub 2020 Jun 14.

Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom. Electronic address:

Introduction: Abnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in some patients with FTD but are poorly characterised.

Methods: We collected data (based on caregiver reports) concerning the prevalence and nature of any behavioural changes related to specific phobias in a cohort of patients representing canonical syndromes of FTD and Alzheimer's disease (AD), relative to healthy older controls. Read More

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http://dx.doi.org/10.1016/j.cortex.2020.05.016DOI Listing

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

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

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

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

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

Value of a Panel of 6 Serum Biomarkers to Differentiate between Healthy Controls and Mild Cognitive Impairment Due to Alzheimer Disease.

Alzheimer Dis Assoc Disord 2020 Jul 7. Epub 2020 Jul 7.

Department of Psychiatry and Psychotherapy, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Background: There is considerable evidence suggesting that inflammatory responses may be involved in the neurodegenerative cascade of Alzheimer disease (AD). Blood-based biomarker analysis of inflammatory markers indicative of dementia could serve as a minimally invasive and easy-to-administer diagnostic tool in primary care.

Material And Methods: The authors quantified 6 markers (brain-derived neurotrophic factor, insulin-like growth factor 1, vascular endothelial growth factor, transforming growth factor-beta type 1, monocyte chemoattractant protein 1, and interleukin-18) in blood serum of 68 healthy blood donors (controls), 42 patients with AD at the dementia stage, 55 patients with AD at the stage of mild cognitive impairment (MCI-AD), and 25 patients with MCI non-AD. Read More

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http://dx.doi.org/10.1097/WAD.0000000000000397DOI Listing

Association of Apolipoprotein E in Lipoprotein Subspecies With Risk of Dementia.

JAMA Netw Open 2020 Jul 1;3(7):e209250. Epub 2020 Jul 1.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Importance: The ε4 allele of the apolipoprotein E (APOE) gene and lower apolipoprotein E (apoE) protein levels in plasma are risk factors for Alzheimer disease, but the underlying biological mechanisms are not fully understood. Half of plasma apoE circulates on high-density lipoproteins (HDLs). Higher apoE levels in plasma HDL were previously found to be associated with lower coronary heart disease risk, but the coexistence of another apolipoprotein, apoC3, modified this lower risk. Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2020.9250DOI Listing

Selective inhibition of NLRP3 inflammasome by designed peptide originating from ASC.

FASEB J 2020 Jul 10. Epub 2020 Jul 10.

Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.

NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is a multiprotein complex which forms within cells in response to various microbial and self-derived triggers. Mutations in the gene encoding NLRP3 cause rare cryopyrin-associated periodic syndromes (CAPS) and growing evidence links NLRP3 inflammasome to common diseases such as Alzheimer´s disease. In order to modulate different stages of NLRP3 inflammasome assembly nine peptides whose sequences correspond to segments of inflammasome components NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) were selected. Read More

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http://dx.doi.org/10.1096/fj.201902938RRDOI Listing

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

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

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

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

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

The overexpression of RBM3 alleviates TBI-induced behaviour impairment and AD-like tauopathy in mice.

J Cell Mol Med 2020 Jul 10. Epub 2020 Jul 10.

Department of Pathophysiology, Key Laboratory of Neurological Diseases of Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The therapeutic hypothermia is an effective tool for TBI-associated brain impairment, but its side effects limit in clinical routine use. Hypothermia up-regulates RNA-binding motif protein 3 (RBM3), which is verified to protect synaptic plasticity. Here, we found that cognitive and LTP deficits, loss of spines, AD-like tau pathologies are displayed one month after TBI in mice. Read More

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http://dx.doi.org/10.1111/jcmm.15555DOI Listing

CD33 and SIGLECL1 Immunoglobulin Superfamily Involved in Dementia.

J Neuropathol Exp Neurol 2020 Jul 10. Epub 2020 Jul 10.

From the Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), Naples, Italy (AR, EV).

Sialic acid-binding immunoglobulin-type lectins, which are predominantly expressed in immune cells, represent a family of immunomodulatory receptors with inhibitory and activating signals, in both healthy and disease states. Genetic factors are important in all forms of dementia, especially in early onset dementia. CD33 was recently recognized as a genetic risk factor for Alzheimer disease (AD). Read More

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http://dx.doi.org/10.1093/jnen/nlaa055DOI Listing

Diagnosed prevalence of Alzheimer's disease and related dementias in Medicare Advantage plans.

Alzheimers Dement (Amst) 2020 5;12(1):e12048. Epub 2020 Jul 5.

Hebrew Senior Life Hinda and Arthur Marcus Institute for Aging Research Boston Massachusetts USA.

Introduction: One-third of Medicare beneficiaries are enrolled in Medicare Advantage (MA). Yet, little is known about MA beneficiaries diagnosed with Alzheimer's disease (AD) and AD-related dementias (AD/ADRD).

Methods: We calculated the prevalence of AD/ADRD diagnoses in 2014 and 2016 in three MA plans. Read More

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http://dx.doi.org/10.1002/dad2.12048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335904PMC

Promising outcome measures of early Alzheimer's dementia in adults with Down syndrome.

Alzheimers Dement (Amst) 2020 5;12(1):e12044. Epub 2020 Jul 5.

Department of Epidemiology School of Public Health Columbia University New York New York USA.

Introduction: Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease (AD) and its associated dementia, warranting the development of strategies to improve early detection when prevention is possible.

Methods: Using a broad battery of neuropsychological assessments, informant interviews, and clinical record review, we evaluated the psychometrics of measures in a large sample of 561 adults with DS. We tracked longitudinal stability or decline in functioning in a subsample of 269 participants over a period of 3 years, all initially without indications of clinically significant aging-related decline. Read More

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http://dx.doi.org/10.1002/dad2.12044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335903PMC

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

Mol Psychiatry 2020 Jul 10. Epub 2020 Jul 10.

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

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

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

Turcz. extract attenuates Alzheimer's disease-associated cognitive deficits and vascular dementia-associated neuronal death.

Anat Cell Biol 2020 Jun;53(2):216-227

Department of Anatomy, College of Medicine, Konyang University, Daejeon, Korea.

Dementia is the common neurodegenerative disorder affecting the elderly, with a progressive cognitive decline and memory loss. Since Alzheimer's disease (AD) and vascular dementia (VD) share key pathologies including oxidative damage, oral supplement of phytochemical medicines, which are well-known for their antioxidant properties, can be a viable therapy for both types of dementia. In this study, the therapeutic potential of the extract (AAE), an oriental drug with multiple medicinal properties, was tested on experimental rat models of AD and VD. Read More

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http://dx.doi.org/10.5115/acb.20.011DOI Listing

Brain Regional Glucose Metabolism, Neuropsychiatric Symptoms, and the Risk of Incident Mild Cognitive Impairment: The Mayo Clinic Study of Aging.

Am J Geriatr Psychiatry 2020 Jun 17. Epub 2020 Jun 17.

Department of Neurology, Barrow Neurological Institute, Phoenix, AZ. Electronic address:

Objective: The authors conducted a prospective cohort study to examine the risk of incident mild cognitive impairment (MCI) as predicted by baseline neuropsychiatric symptoms (NPS) and brain regional glucose metabolic dysfunction.

Methods: About 1,363 cognitively unimpaired individuals (52.8% males) aged ≥50 years were followed for a median of 4. Read More

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

MicroRNAs Related to Cognitive Impairment After Hearing Loss.

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

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

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

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

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

Novel Blood-Derived Extracellular Vesicle-Based Biomarkers in Alzheimer's Disease Identified by Proximity Extension Assay.

Biomedicines 2020 Jul 7;8(7). Epub 2020 Jul 7.

Department of Clinical Medicine, Aalborg University, DK-9000 Aalborg, Denmark.

Easily accessible biomarkers for Alzheimer's dementia (AD) are lacking and established clinical markers are limited in applicability. Blood is a common biofluid for biomarker discoveries, and extracellular vesicles (EVs) may provide a matrix for exploring AD related biomarkers. Thus, we investigated proteins related to neurological and inflammatory processes in plasma and EVs. Read More

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http://dx.doi.org/10.3390/biomedicines8070199DOI Listing

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The promotion of physical activity for the prevention of Alzheimer's disease in adults with Down Syndrome: Rationale and design for a 12 Month randomized trial.

Contemp Clin Trials Commun 2020 Sep 30;19:100607. Epub 2020 Jun 30.

Department of Internal Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA.

Nearly all individuals with Down Syndrome (DS) display pathology associated with Alzheimer's disease (AD) beginning as early as age 30. Previous research in typically developed adults suggests that increased moderate-to-vigorous physical activity (MVPA) may improve cognitive function and protect against age-related structural and functional changes in the brain; however, the potential impact of increased MVPA on the development of AD in adults with DS has not been evaluated. Despite the potential positive impact of MVPA on cognition and AD risk, participation in MVPA among young adults with DS is low. Read More

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http://dx.doi.org/10.1016/j.conctc.2020.100607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334572PMC
September 2020

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

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

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

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

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

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

Calcium Channel Blockade Ameliorates Endoplasmic Reticulum Stress in the Hippocampus Induced by Amyloidopathy in the Entorhinal Cortex.

Iran J Pharm Res 2019 ;18(3):1466-1476

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

Entorhinal cortex (EC) is one of the first cerebral regions affected in Alzheimer's disease (AD). The pathology propagates to neighboring cerebral regions through a prion-like mechanism. In AD, intracellular calcium dyshomeostasis is associated with endoplasmic reticulum (ER) stress. Read More

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http://dx.doi.org/10.22037/ijpr.2019.111532.13216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934951PMC
January 2019

Cerebrovascular reactivity in cerebral amyloid angiopathy, Alzheimer disease, and mild cognitive impairment.

Neurology 2020 Jul 8. Epub 2020 Jul 8.

Department of Clinical Neurosciences, University of Calgary, Calgary, Canada

Objective: To assess cerebrovascular reactivity in response to a visual task in participants with cerebral amyloid angiopathy (CAA), Alzheimer's disease (AD), and mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI).

Methods: Prospective cohort study including 40 CAA, 22 AD, 27 MCI, and 25 healthy controls. Each participant underwent a visual fMRI task using a contrast-reversing checkerboard stimulus. Read More

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http://dx.doi.org/10.1212/WNL.0000000000010201DOI Listing

Microglial cathepsin B and Porphyromonas gingivalis gingipains as potential therapeutic targets for sporadic Alzheimer's disease.

CNS Neurol Disord Drug Targets 2020 Jul 8. Epub 2020 Jul 8.

OBT Research Center, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582. Japan.

Many efforts have been made to develop therapeutic agents for Alzheimer's disease (AD) based on the amyloid cascade hypothesis, but there is no effective therapeutic agent at present. Now much attention has been paid to infiltrated pathogens in the brain as a trigger of AD. These pathogens, or their virulence factors, may directly cross a weakened blood- brain barrier, reach the brain and cause neurological damage by eliciting neuroinflammation. Read More

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http://dx.doi.org/10.2174/1871527319666200708125130DOI Listing

Impact of Cannabis-Based Medicine on Alzheimer's disease by Focusing on the Amyloid β- Modifications: A Systematic Study.

CNS Neurol Disord Drug Targets 2020 Jul 8. Epub 2020 Jul 8.

Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur. Iran.

Introduction: Deposition of amyloid-beta (Aβ) peptide in the brain is the leading source of the onset and progression of Alzheimer's disease (AD). Recent studies have suggested that anti-amyloidogenic agents may be a suitable therapeutic strategy for AD.

Aim: The current review was proposed to address the beneficial effects of cannabis-based drugs for the treatment of AD, focusing primarily on Aβ modifications. Read More

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http://dx.doi.org/10.2174/1871527319666200708130745DOI Listing

Animal-Assisted Therapy as a Non-Pharmacological Approach in Alzheimer's Disease: A Retrospective Study.

Animals (Basel) 2020 Jul 6;10(7). Epub 2020 Jul 6.

Department of Veterinary Medicine and Animal Productions, Federico II University of Naples, 80134 Naples, Italy.

Recently, many efforts have been made to assess the effectiveness of non-pharmacological therapies as an alternative or supportive option to conventional approaches. Specifically, animal-assisted therapy (AAT) has recently raised a great interest and large research efforts. This work represents a retrospective study carried out over seven years (from 2012 to 2019) in 127 patients with mild-to-moderate Alzheimer's disease. Read More

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http://dx.doi.org/10.3390/ani10071142DOI Listing

Affective temperament traits may explain high expressed emotion in caregivers of patients with Alzheimer's disease.

Psychogeriatrics 2020 Jul 7. Epub 2020 Jul 7.

Department of Psychiatry, Adnan Menderes University, Aydin, Turkey.

Background: The negative interactions between Alzheimer's disease (AD) patients and their caregivers may provoke criticism, hostility, and emotional overinvolvement that characterise highly expressed emotion (EE) attitudes. In this study, we hypothesised that affective temperament traits of AD caregivers are related to their high EE levels independent from other patient and caregiver characteristics.

Methods: Eighty AD patients were assessed through Clinical Dementia Rating Scale (CDR), and Mini-Mental State Examination. Read More

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http://dx.doi.org/10.1111/psyg.12588DOI Listing

Modulation of Kv3.1/Kv3.2 promotes gamma oscillations by rescuing Aβ-induced desynchronization of fast-spiking interneuron firing in an AD mouse model in vitro.

J Physiol 2020 Jul 7. Epub 2020 Jul 7.

Neuronal Oscillations Laboratory.

Key Points: Gamma oscillations (30-80 Hz) are important for cognitive functions and depend on the synchronized activity of fast-spiking interneurons (FSN), which is crucial for network stability. Gamma oscillations are degraded in Alzheimer's disease (AD) patients exhibiting cognitive impairment, with the degree of cognitive decline correlating with the severity of gamma disruption in response to neurotoxic amyloid-beta peptide (Aβ). Small molecule compounds EX15 and RE01 modulate Kv3. Read More

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http://dx.doi.org/10.1113/JP279718DOI Listing

Chronic Administration of Scopolamine Increased GSK3βP9, Beta Secretase, Amyloid Beta, and Oxidative Stress in the Hippocampus of Wistar Rats.

Mol Neurobiol 2020 Jul 7. Epub 2020 Jul 7.

Laboratorio de Biofísica y Biocatálisis, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340, Mexico, Mexico.

The increase of amyloid beta (Aβ) release and hyperphosphorylation of Tau protein represents the main events related to Alzheimer's disease (AD). Furthermore, the sporadic type represents the most common form of AD. Therefore, the establishment of a non-transgenic animal model that resembles the characteristics of the disease is of particular importance. Read More

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http://dx.doi.org/10.1007/s12035-020-02009-xDOI Listing

Synonymous variants associated with Alzheimer disease in multiplex families.

Neurol Genet 2020 Aug 8;6(4):e450. Epub 2020 Jun 8.

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain (M.E.A., B.V., R.L., P.L.J., R.M., I.S.-M., C.R.); The Gertrude H. Sergievsky Center (M.T., D.R.-D., R.L., R.M., C.R.); Department of Neurology (P.L.J., R.M., C.R.); Department of Epidemiology (R.M., C.R.); Department of Psychiatry (R.M.), Columbia University, New York; Department of Pathology and Cell Biology (M.E.A., I.S.-M.), Columbia University, New York; Rush Alzheimer's Disease Center (D.A.B.); Department of Neurological Sciences (D.A.B.); Department of Pathology (D.A.B.), Rush University Medical Center, Chicago, IL; Center for Innovation in Brain Science , Departments of Pharmacology and Neurology , University of Arizona College of Medicine (M.T.), Tucson; Department of Medicine (R.L.), College of Physicians and Surgeons, Columbia University, New York, NY; School of Medicine (M.M.), Mother and Teacher Pontifical Catholic University, Santiago, Dominican Republic; and The Krembil Centre for Neuroinformatics (D.F.), Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Objective: Synonymous variants can lead to disease; nevertheless, the majority of sequencing studies conducted in Alzheimer disease (AD) only assessed coding variation.

Methods: To detect synonymous variants modulating AD risk, we conducted a whole-genome sequencing study on 67 Caribbean Hispanic (CH) families multiply affected by AD. Identified disease-associated variants were further assessed in an independent cohort of CHs, expression quantitative trait locus (eQTL) data, brain autopsy data, and functional experiments. Read More

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http://dx.doi.org/10.1212/NXG.0000000000000450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323483PMC

Discovery of a Selective 6-Hydroxy-1, 4-Diazepan-2-one Containing Butyrylcholinesterase Inhibitor by Virtual Screening and MM-GBSA Rescoring.

Dose Response 2020 Apr-Jun;18(2):1559325820938526. Epub 2020 Jun 29.

School of Pharmacy, China Pharmaceutical University, Nanjing, China.

Alzheimer disease (AD) is the most common form of dementia characterized by the loss of cognitive abilities through the death of central neuronal cells. In this study, structure-based virtual screens of 2 central nervous system-targeted libraries followed by molecular mechanics/generalized born surface area rescoring were performed to discover novel, selective butyrylcholinesterase (BChE) inhibitors, which are one of the most effective therapeutic strategies for the treatments in late-stage AD. Satisfyingly, compound 5 was identified as a highly selective low micromolar inhibitor of BChE (BChE IC = 1. Read More

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http://dx.doi.org/10.1177/1559325820938526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324897PMC

Diagnostic and prognostic value of EEG in prodromal dementia with Lewy bodies.

Neurology 2020 Jul 7. Epub 2020 Jul 7.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Objective: Early biomarkers for dementia with Lewy bodies (DLB) are still lacking. To determine whether electroencephalography (EEG) differentiates the prodromal phase of DLB from other causes of mild cognitive impairment (MCI) and whether EEG is predictive for time to conversion from MCI to DLB, we compared EEGs and clinical follow-up of patients with MCI due to DLB with MCI due to Alzheimer's disease (MCI-AD).

Methods: We compared 37 MCI-patients who developed DLB during follow-up and/or had an abnormal I-PF-CIT SPECT scan (MCI-DLB) with 67 age-matched MCI-AD-patients. Read More

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http://dx.doi.org/10.1212/WNL.0000000000009977DOI Listing

Lifetime cumulative incidence of dementia in a community-dwelling elderly population in Japan.

Neurology 2020 Jul 7. Epub 2020 Jul 7.

From the Departments of Epidemiology and Public Health (D.Y., J.H., T.H., Y.F., E.O., T.N.), Neuropsychiatry (T.O., S.K.), Center for Cohort Studies (M.S., S.S.), and Medicine and Clinical Science (Y.H., T.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: To estimate the lifetime cumulative incidence of dementia and its subtypes from a community-dwelling elderly population in Japan.

Methods: A total of 1,193 community-dwelling Japanese individuals without dementia, aged 60 years or older, were followed up prospectively for 17 years. The cumulative incidence of dementia was estimated based on a death- and dementia-free survival function and the hazard functions of dementia at each year, which were computed by using a Weibull proportional hazards model. Read More

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http://dx.doi.org/10.1212/WNL.0000000000009917DOI Listing

Predictors of Disease Progression in Early-Onset Alzheimer's Dementia: A Retrospective Cohort Study.

J Am Med Dir Assoc 2020 Jul 4. Epub 2020 Jul 4.

Psychiatry for Elderly, Department of Health Sciences, College of Life Sciences, George Davies Centre, Leicester, United Kingdom.

Objectives: Early-onset Alzheimer's disease (EOAD), defined as onset of AD before the age of 65 years, is less common than the late-onset type, and little is known about the factors affecting disease progression. The aim of the study was to investigate factors influencing disease progression in people with EOAD.

Design: Retrospective cohort study. Read More

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http://dx.doi.org/10.1016/j.jamda.2020.05.016DOI Listing

Therapeutic Cocktail Approach for Treatment of Hyperhomocysteinemia in Alzheimer's Disease.

Cell Med 2018 25;10:2155179017722280. Epub 2018 Jan 25.

Department of Psychiatry and Behavioral Neurosciences, Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

In the United States, Alzheimer's disease (AD) is the most common cause of dementia, accompanied by substantial economic and emotional costs. During 2015, more than 15 million family members who provided care to AD patients had an estimated total cost of 221 billion dollars. Recent studies have shown that elevated total plasma levels of homocysteine (tHcy), a condition known as hyperhomocysteinemia (HHcy), is a risk factor for AD. Read More

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http://dx.doi.org/10.1177/2155179017722280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172991PMC
January 2018

Inflammatory pathway analytes predicting rapid cognitive decline in MCI stage of Alzheimer's disease.

Ann Clin Transl Neurol 2020 Jul 7. Epub 2020 Jul 7.

Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, Ohio, 44195.

Objective: To determine the inflammatory analytes that predict clinical progression and evaluate their performance against biomarkers of neurodegeneration.

Methods: A longitudinal study of MCI-AD patients in a Discovery cohort over 15 months, with replication in the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort over 36 months. Fifty-three inflammatory analytes were measured in the CSF and plasma with a RBM multiplex analyte platform. Read More

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http://dx.doi.org/10.1002/acn3.51109DOI Listing

MicroRNA-195 rescues ApoE4-induced cognitive deficits and lysosomal defects in Alzheimer's disease pathogenesis.

Mol Psychiatry 2020 Jul 6. Epub 2020 Jul 6.

James J Peters VA Medical Center, Research & Development, Bronx, NY, 10468, USA.

Our recent findings link the apolipoprotein E4 (ApoE4)-specific changes in brain phosphoinositol biphosphate (PIP) homeostasis to the susceptibility of developing Alzheimer's Disease (AD). In the present study, we have identified miR-195 as a top micro-RNA candidate involved in the ApoE/PIP pathway using miRNA profiles in human ROSMAP datasets and mouse microarray studies. Further validation studies have demonstrated that levels of miR-195 are significantly lower in human brain tissue of ApoE4 patients with clinical diagnosis of mild cognitive impairment (MCI) or early AD when compared to ApoE4 subjects. Read More

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http://dx.doi.org/10.1038/s41380-020-0824-3DOI Listing

β-amyloid and tau drive early Alzheimer's disease decline while glucose hypometabolism drives late decline.

Commun Biol 2020 Jul 6;3(1):352. Epub 2020 Jul 6.

Sanders-Brown Center on Aging, University of Kentucky, 307 Sanders-Brown Building, 800 S. Limestone Street, Lexington, KY, 40506-0230, USA.

Clinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer's disease (AD), suggesting that Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD. Read More

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http://dx.doi.org/10.1038/s42003-020-1079-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338410PMC

Neuropathological features associated with basal forebrain atrophy in Alzheimer's disease.

Neurology 2020 Jul 6. Epub 2020 Jul 6.

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

Objective: To study the neuropathological correlates of cholinergic basal forebrain atrophy as determined using ante-mortem MRI in the Alzheimer's disease (AD) spectrum.

Methods: We determined associations between basal forebrain (BF) volume from antemortem MRI brain scans and post-mortem assessment of neuropathological features, including neuritic plaques, neurofibrillary tangles (NFT), Lewy body (LB) pathology, and TDP-43, in 64 cases of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. For comparison, we assessed neuropathological features associated with hippocampal and parahippocampal gyrus atrophy. Read More

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http://dx.doi.org/10.1212/WNL.0000000000010192DOI Listing

Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/γ-secretase at the cell surface.

Elife 2020 Jul 7;9. Epub 2020 Jul 7.

Laboratory for Membrane Trafficking, VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium.

γ-Secretase is a multi-subunit enzyme whose aberrant activity is associated with Alzheimer's disease and cancer. While its structure is atomically resolved, γ-secretase localization in the membrane in situ relies mostly on biochemical data. Here, we combined fluorescent tagging of γ-secretase subunits with super-resolution microscopy in fibroblasts. Read More

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http://dx.doi.org/10.7554/eLife.56679DOI Listing

Disturbed balance in the expression of MMP9 and TIMP3 in cerebral amyloid angiopathy-related intracerebral haemorrhage.

Acta Neuropathol Commun 2020 Jul 6;8(1):99. Epub 2020 Jul 6.

Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of the amyloid β (Aβ) protein in the cerebral vasculature and poses a major risk factor for the development of intracerebral haemorrhages (ICH). However, only a minority of patients with CAA develops ICH (CAA-ICH), and to date it is unclear which mechanisms determine why some patients with CAA are more susceptible to haemorrhage than others. We hypothesized that an imbalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) contributes to vessel wall weakening. Read More

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http://dx.doi.org/10.1186/s40478-020-00972-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336459PMC

Cathepsin D regulates cerebral Aβ42/40 ratios via differential degradation of Aβ42 and Aβ40.

Alzheimers Res Ther 2020 Jul 6;12(1):80. Epub 2020 Jul 6.

Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, 92697, USA.

Background: Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid β-protein (Aβ) and the microtubule-associated protein, tau, and has been genetically linked to late-onset Alzheimer disease (AD). Here, we sought to examine the consequences of genetic deletion of CatD on Aβ proteostasis in vivo and to more completely characterize the degradation of Aβ42 and Aβ40 by CatD.

Methods: We quantified Aβ degradation rates and levels of endogenous Aβ42 and Aβ40 in the brains of CatD-null (CatD-KO), heterozygous null (CatD-HET), and wild-type (WT) control mice. Read More

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http://dx.doi.org/10.1186/s13195-020-00649-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339583PMC

IPSC-Derived Neuronal Cultures Carrying the Alzheimer's Disease Associated R47H Variant Enables the Construction of an Aβ-Induced Gene Regulatory Network.

Int J Mol Sci 2020 Jun 25;21(12). Epub 2020 Jun 25.

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.

Genes associated with immune response and inflammation have been identified as genetic risk factors for late-onset Alzheimer´s disease (LOAD). The rare R47H variant within triggering receptor expressed on myeloid cells 2 (TREM2) has been shown to increase the risk for developing Alzheimer's disease (AD) 2-3-fold. Here, we report the generation and characterization of a model of late-onset Alzheimer's disease (LOAD) using lymphoblast-derived induced pluripotent stem cells (iPSCs) from patients carrying the TREM2 R47H mutation, as well as from control individuals without dementia. Read More

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http://dx.doi.org/10.3390/ijms21124516DOI Listing

Enlightening the advancements in electrochemical bioanalysis for the diagnosis of Alzheimer's disease and other neurodegenerative disorders.

J Pharm Biomed Anal 2020 Jun 21;189:113437. Epub 2020 Jun 21.

Department of Analytical Chemistry, Faculty of Chemical Sciences, Complutense University of Madrid, Madrid, 28040, Spain. Electronic address:

Neurodegenerative disorders (NDD), and particularly Alzheimer's disease (AD), are one of the greatest challenges facing our current medicine and society because of its increasing incidence and the high burden imposed both on patients' families and health systems. Despite this, their accurate diagnosis, mostly conducted by cerebrospinal fluid (CSF) analysis or neuroimaging techniques, costly, time-consuming, and unaffordable for most of the population, remains a complex task. In this situation, electrochemical biosensors are flourishing as promising alternative tools for the simple, fast, and low-cost diagnosis of NDD/AD. Read More

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http://dx.doi.org/10.1016/j.jpba.2020.113437DOI Listing

Spermidine Intake is Associated with Cortical Thickness and Hippocampal Volume in Older Adults.

Neuroimage 2020 Jul 3:117132. Epub 2020 Jul 3.

Department of Neurology, University Medicine Greifswald, Greifswald, Germany; German Center for Neurodegenerative Diseases (DZNE) Standort Greifswald, Greifswald, Germany. Electronic address:

Background: The natural polyamine spermidine, known to be important for cellular function, decreases during aging. Previous research has demonstrated beneficial impact of spermidine intake on memory functions in both animal models and humans, suggesting that spermidine may be a preventive approach to delay age-related cognitive decline and possibly even Alzheimer's disease (AD). However, the association of spermidine intake with brain health in humans is still unknown. Read More

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http://dx.doi.org/10.1016/j.neuroimage.2020.117132DOI Listing

Diabetes-Related Topics in an Online Forum for Caregivers of Individuals Living With Alzheimer Disease and Related Dementias: Qualitative Inquiry.

J Med Internet Res 2020 Jul 6;22(7):e17851. Epub 2020 Jul 6.

Center on Smart and Connected Health Technologies, School of Nursing, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.

Background: Diabetes and Alzheimer disease and related dementias (ADRD) are the seventh and sixth leading causes of death in the United States, respectively, and they coexist in many older adults. Caring for a loved one with both ADRD and diabetes is challenging and burdensome.

Objective: This study aims to explore diabetes-related topics in the Alzheimer's Association ALZConnected caregiver forum by family caregivers of persons living with ADRD. Read More

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http://dx.doi.org/10.2196/17851DOI Listing

[Study on mechanisms of anti-Alzheimer's disease action of absorbed components of Gardeniae Fructus based on network pharmacology].

Zhongguo Zhong Yao Za Zhi 2020 Jun;45(11):2601-2610

Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine Nanchang 330004, China.

Gardeniae Fructus has the traditional effects of promoting intelligence and inducing resuscitation, but its mechanism is unclear. In this study, the relationship between Gardeniae Fructus's traditional effect of promoting intelligence and inducing resuscitation and anti-Alzheimer's disease effect was taken as the starting point to investigate the anti-Alzheimer's disease mechanism of the major absorbed components in Gardeniae Fructus by the network pharmacology method. The network pharmacology research model of "absorbed composition-target-pathway-disease" was adopted. Read More

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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200204.401DOI Listing