769 results match your criteria 5xfad mice

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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Cereblon regulates the proteotoxicity of tau by tuning the chaperone activity of DNAJA1.

J Neurosci 2021 May 7. Epub 2021 May 7.

Laboratory of Molecular Neurobiology

Protein aggregation can induce explicit neurotoxic events that trigger a number of presently untreatable neurodegenerative disorders. Chaperones, on the other hand, play a neuroprotective role due to their ability to unfold and refold abnormal proteins. Progressive nature of neurotoxic events makes it important to discover endogenous factors that affect pathological and molecular phenotypes of neurodegeneration in animal models. Read More

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Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease.

J Vis Exp 2021 Apr 19(170). Epub 2021 Apr 19.

Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology and NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University;

Alzheimer's disease (AD) is a neurodegenerative disease that contributes to 60-70% dementia around the world. One of the hallmarks of AD undoubtedly lies on accumulation of amyloid-β (Aβ) in the brain. Aβ is produced from the proteolytic cleavage of the beta-amyloid precursor protein (APP) by β-secretase and γ-secretase. Read More

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Prolonged Treatment with Centella asiatica Improves Memory, Reduces Amyloid-β Pathology, and Activates NRF2-Regulated Antioxidant Response Pathway in 5xFAD Mice.

J Alzheimers Dis 2021 Apr 28. Epub 2021 Apr 28.

Department of Neurology, Oregon Health & Science University, Portland, OR, USA.

Background: The medicinal herb Centella asiatica has been long been used for its neuroprotective and cognitive enhancing effects. We have previously shown that two weeks of treatment with a water extract of Centella asiatica (CAW) improves cognition and activates the endogenous antioxidant response pathway without altering amyloid-β (Aβ) plaque burden.

Objective: Here, we assess the effect of long-term treatment of CAW in the 5xFAD mouse model of Aβ accumulation. Read More

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Impact of Gut Microbiome Manipulation in 5xFAD Mice on Alzheimer's Disease-Like Pathology.

Microorganisms 2021 Apr 13;9(4). Epub 2021 Apr 13.

Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

The gut brain axis seems to modulate various psychiatric and neurological disorders such as Alzheimer's disease (AD). Growing evidence has led to the assumption that the gut microbiome might contribute to or even present the nucleus of origin for these diseases. In this regard, modifiers of the microbial composition might provide attractive new therapeutics. Read More

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Neuronal and Astrocytic Extracellular Vesicle Biomarkers in Blood Reflect Brain Pathology in Mouse Models of Alzheimer's Disease.

Cells 2021 Apr 23;10(5). Epub 2021 Apr 23.

Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 212241, USA.

Circulating neuronal extracellular vesicles (NEVs) of Alzheimer's disease (AD) patients show high Tau and β-amyloid (Aβ) levels, whereas their astrocytic EVs (AEVs) contain high complement levels. To validate EV proteins as AD biomarkers, we immunocaptured NEVs and AEVs from plasma collected from fifteen wild type (WT), four 2xTg-AD, nine 5xFAD, and fifteen 3xTg-AD mice and assessed biomarker relationships with brain tissue levels. NEVs from 3xTg-AD mice had higher total Tau ( = 0. Read More

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Alterations in the Gut-Microbial-Inflammasome-Brain Axis in a Mouse Model of Alzheimer's Disease.

Cells 2021 Apr 1;10(4). Epub 2021 Apr 1.

Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by memory loss and cognitive decline, is a major cause of death and disability among the older population. Despite decades of scientific research, the underlying etiological triggers are unknown. Recent studies suggested that gut microbiota can influence AD progression; however, potential mechanisms linking the gut microbiota with AD pathogenesis remain obscure. Read More

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The Neuroprotective Beta Amyloid Hexapeptide Core Reverses Deficits in Synaptic Plasticity in the 5xFAD APP/PS1 Mouse Model.

Front Mol Neurosci 2021 12;14:576038. Epub 2021 Apr 12.

Department of Cell & Molecular Biology, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, HI, United States.

Alzheimer's disease (AD) is the most common cause of dementia in the aging population. Evidence implicates elevated soluble oligomeric Aβ as one of the primary triggers during the prodromic phase leading to AD, effected largely via hyperphosphorylation of the microtubule-associated protein tau. At low, physiological levels (pM-nM), however, oligomeric Aβ has been found to regulate synaptic plasticity as a neuromodulator. Read More

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Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy.

Nature 2021 Apr 28. Epub 2021 Apr 28.

Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.

Alzheimer's disease (AD) is the most prevalent cause of dementia. Although there is no effective treatment for AD, passive immunotherapy with monoclonal antibodies against amyloid beta (Aβ) is a promising therapeutic strategy. Meningeal lymphatic drainage has an important role in the accumulation of Aβ in the brain, but it is not known whether modulation of meningeal lymphatic function can influence the outcome of immunotherapy in AD. Read More

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Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice.

Acta Neuropathol Commun 2021 Apr 23;9(1):74. Epub 2021 Apr 23.

Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute, Room: 241, 1501 San Pablo Street, Los Angeles, CA, 90033, USA.

Introduction: Traumatic brain injury (TBI) is considered as the most robust environmental risk factor for Alzheimer's disease (AD). Besides direct neuronal injury and neuroinflammation, vascular impairment is also a hallmark event of the pathological cascade after TBI. However, the vascular connection between TBI and subsequent AD pathogenesis remains underexplored. Read More

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Alzheimer's pathology causes impaired inhibitory connections and reactivation of spatial codes during spatial navigation.

Cell Rep 2021 Apr;35(3):109008

Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address:

Synapse loss and altered synaptic strength are thought to underlie cognitive impairment in Alzheimer's disease (AD) by disrupting neural activity essential for memory. While synaptic dysfunction in AD has been well characterized in anesthetized animals and in vitro, it remains unknown how synaptic transmission is altered during behavior. By measuring synaptic efficacy as mice navigate in a virtual reality task, we find deficits in interneuron connection strength onto pyramidal cells in hippocampal CA1 in the 5XFAD mouse model of AD. Read More

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A delta-secretase-truncated APP fragment activates CEBPB, mediating Alzheimer's disease pathologies.

Brain 2021 Apr 20. Epub 2021 Apr 20.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Amyloid-β precursor protein (APP) is sequentially cleaved by secretases and generates amyloid-β, the major components in senile plaques in Alzheimer's disease. APP is upregulated in human Alzheimer's disease brains. However, the molecular mechanism of how APP contributes to Alzheimer's disease pathogenesis remains incompletely understood. Read More

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A novel nutritional mixture, MBN, prevents memory impairment via inhibiting NLRP3 inflammasome formation in 5xFAD transgenic mice.

Nutr Neurosci 2021 Apr 20:1-8. Epub 2021 Apr 20.

Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, Republic of Korea.

Objectives: Amyloid beta (Aβ)-induced abnormal neuroinflammation is recognized as a major pathological factor of Alzheimer's disease (AD), which results in memory impairment. Inhibition of excessive neuroinflammation mediated by Aβ is considered a promising strategy to ameliorate AD symptoms. To regulate the inflammatory response, nutritional and dietary supplements have been used for centuries. Read More

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Subtle genomic DNA damage induces intraneuronal production of amyloid-β (1-42) by increasing β-secretase activity.

FASEB J 2021 May;35(5):e21569

Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Aberrant accumulation of amyloid-β (Aβ) in brain is the major trigger for pathogenesis in Alzheimer's disease (AD). It is imperative to understand how Aβ attains such toxic levels in the brain parenchyma. We detected that a subtle and tolerable amount of DNA damage, related to aging, increased intraneuronal Aβ production both in cultured neuron and in cortex of rodent brain. Read More

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A regional and cellular analysis of the early intracellular and extracellular accumulation of Aβ in the brain of 5XFAD mice.

Neurosci Lett 2021 May 12;754:135869. Epub 2021 Apr 12.

Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology (CfNN), University of Modena and Reggio Emilia, 41125, Modena, Italy. Electronic address:

Intracellular Aβ (iAβ) expression, extracellular Aβ (eAβ) plaque formation and microglial reactivity are characteristic neuropathological events of Alzheimer's disease (AD) and have been detected in several transgenic mouse models of this disease. In this work we decided to investigate the early (2-7 months of age) development of these phenomena at both regional and cellular levels in 5XFAD mice, a severe transgenic mouse model of AD. We demonstrated that 1) Aβ pathology develops in many but not all brain regions, 2) iAβ is transient and almost always followed by eAβ in grey matter regions, and the respective levels are roughly proportional, and 3) in about 1/3 of the grey matter regions with Aβ pathology and in several white matter regions, eAβ plaques can appear where no iAβ-positive structures were detected. Read More

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affects oxidative stress and pyroptosis in hippocampal neurons of Alzheimer's disease mouse model by regulating the Nrf2 pathway.

Lin Cheng Wei Zhang

Exp Ther Med 2021 Jun 26;21(6):557. Epub 2021 Mar 26.

Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.

Studies have confirmed that is associated with diseases associated with the nervous system, including Alzheimer's disease (AD). However, the role of in the pathogenesis of AD has not been clarified. To investigate the effect of on brain tissue damage and cognitive function in AD mice and its possible mechanism, 5XFAD transgenic mice were used as AD model mice and in the brain was overexpressed by transfection of a lentiviral containing a specific targeting gene into the bilateral hippocampus of mice. Read More

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Ginkgo biloba extract improves cognitive function and increases neurogenesis by reducing Aβ pathology in 5×FAD mice.

Am J Transl Res 2021 15;13(3):1471-1482. Epub 2021 Mar 15.

Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China No 17 Lvjiang Road, Hefei 230001, Anhui, China.

Previous studies have indicated that the generation of newborn hippocampal neurons is impaired in the early phase of Alzheimer's disease (AD). A potential therapeutic strategy being pursued for the treatment of AD is increasing the number of newborn neurons in the adult hippocampus. Recent studies have demonstrated that ginkgo biloba extract (EGb 761) plays a neuroprotective role by preventing memory loss in many neurodegenerative diseases. Read More

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Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis.

Brain Behav Immun 2021 Apr 9. Epub 2021 Apr 9.

Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China; Department of Food Science, Cornell University, Ithaca, NY 14853, United States. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive deficits and psychiatric symptoms. The gut microbiota-brain axis plays a pivotal role during AD development, which could target nutritional intervention. The prebiotic mannan oligosaccharide (MOS) has been reported to reshape the gut microbiome and enhanced the formation of the neuroprotective metabolites short-chain fatty acids (SCFAs). Read More

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PLD3 is a neuronal lysosomal phospholipase D associated with β-amyloid plaques and cognitive function in Alzheimer's disease.

PLoS Genet 2021 Apr 8;17(4):e1009406. Epub 2021 Apr 8.

Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.

Phospholipase D3 (PLD3) is a protein of unclear function that structurally resembles other members of the phospholipase D superfamily. A coding variant in this gene confers increased risk for the development of Alzheimer's disease (AD), although the magnitude of this effect has been controversial. Because of the potential significance of this obscure protein, we undertook a study to observe its distribution in normal human brain and AD-affected brain, determine whether PLD3 is relevant to memory and cognition in sporadic AD, and to evaluate its molecular function. Read More

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Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: A Comparative study with donepezil.

Br J Pharmacol 2021 Apr 5. Epub 2021 Apr 5.

Pharmacology Section. Department of Pharmacology, Toxicology and Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, and Institut de Neurociències, University of Barcelona, Av. Joan XXIII, 27-31, E-08028, Barcelona, Spain.

Background And Purpose: The development of effective therapeutic strategies against Alzheimer's disease (AD) remains a challenge. I2 Imidazoline receptors (I2-IR) ligands have a neuroprotective role in AD. Moreover, co-treatment of acetylcholinesterase inhibitors with neuroprotective agents has shown better effects on the prevention of dementia. Read More

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Age, sex, and cerebral microbleeds in EFAD Alzheimer disease mice.

Neurobiol Aging 2021 Feb 28;103:42-51. Epub 2021 Feb 28.

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Departments of Neurobiology and Molecular Biology, The Dornsife College, University of Southern California, Los Angeles, CA, USA. Electronic address:

Cerebral microbleeds (MBs) increase at later ages in association with increased cognitive decline and Alzheimer Disease (AD). MB prevalence is also increased by APOE4 and hypertension. In EFAD mice (5XFAD/human APOE), cerebral cortex MBs are most prevalent in E4 females at 6 months, paralleling plaque amyloid. Read More

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February 2021

Voluntary Wheel Running Did Not Alter Gene Expression in 5xfad Mice, but in Wild-Type Animals Exclusively after One-Day of Physical Activity.

Cells 2021 Mar 20;10(3). Epub 2021 Mar 20.

Working Group Healthy Aging and Neurodegeneration, Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.

Physical activity is considered a promising preventive intervention to reduce the risk of developing Alzheimer's disease (AD). However, the positive effect of therapeutic administration of physical activity has not been proven conclusively yet, likely due to confounding factors such as varying activity regimens and life or disease stages. To examine the impact of different routines of physical activity in the early disease stages, we subjected young 5xFAD and wild-type mice to 1-day (acute) and 30-day (chronic) voluntary wheel running and compared them with age-matched sedentary controls. Read More

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The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice.

Int J Mol Sci 2021 Mar 9;22(5). Epub 2021 Mar 9.

Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.

Alzheimer's disease (AD) is the most common form of dementia. In particular, neuroinflammation, mediated by microglia cells but also through CD8+ T-cells, actively contributes to disease pathology. Leukotrienes are involved in neuroinflammation and in the pathological hallmarks of AD. Read More

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Reduction of Amyloid Burden by Proliferated Homeostatic Microglia in -Infected Alzheimer's Disease Model Mice.

Int J Mol Sci 2021 Mar 9;22(5). Epub 2021 Mar 9.

Department of Tropical Medicine and Parasitology, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul 03080, Korea.

In this study, we confirmed that the number of resident homeostatic microglia increases during chronic infection. Given that the progression of Alzheimer's disease (AD) worsens with the accumulation of amyloid β (Aβ) plaques, which are eliminated through microglial phagocytosis, we hypothesized that -induced microglial proliferation would reduce AD progression. Therefore, we investigated the association between microglial proliferation and Aβ plaque burden using brain tissues isolated from 5XFAD AD mice (AD group) and -infected AD mice (AD + Toxo group). Read More

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Sodium butyrate ameliorates the impairment of synaptic plasticity by inhibiting the neuroinflammation in 5XFAD mice.

Chem Biol Interact 2021 May 27;341:109452. Epub 2021 Mar 27.

College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin, 300071, China. Electronic address:

Current strategies for the treatment of Alzheimer's disease (AD) focus on the pathology in the later stages of disease progression. Early microglia abnormality and β-amyloid (Aβ) deposition trigger disease development before identical symptoms emerge, which leads to poor clinical treatment effects in the later stages. In the early stage of disease progression, microglia in brains of 5XFAD mice have been activated by Aβ plaques to secrete more pro-inflammatory cytokines. Read More

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PIP Improves Cerebral Blood Flow in a Mouse Model of Alzheimer's Disease.

Function (Oxf) 2021 22;2(2):zqab010. Epub 2021 Feb 22.

Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT, USA.

Alzheimer's disease (AD) is a leading cause of dementia and a substantial healthcare burden. Despite this, few treatment options are available for controlling AD symptoms. Notably, neuronal activity-dependent increases in cortical cerebral blood flow (CBF; functional hyperemia) are attenuated in AD patients, but the associated pathological mechanisms are not fully understood at the molecular level. Read More

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February 2021

Acitretin reverses early functional network degradation in a mouse model of familial Alzheimer's disease.

Sci Rep 2021 Mar 23;11(1):6649. Epub 2021 Mar 23.

Focus Program Translational Neurosciences, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

Aberrant activity of local functional networks underlies memory and cognition deficits in Alzheimer's disease (AD). Hyperactivity was observed in microcircuits of mice AD-models showing plaques, and also recently in early stage AD mutants prior to amyloid deposition. However, early functional effects of AD on cortical microcircuits remain unresolved. Read More

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A nuclear factor-kappa B inhibiting peptide suppresses innate immune receptors and gliosis in a transgenic mouse model of Alzheimer's disease.

Biomed Pharmacother 2021 Jun 20;138:111405. Epub 2021 Mar 20.

Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, United States; Provaidya LLC, Indianapolis, IN, United States. Electronic address:

A disproportionate increase in activated nuclear factor-kappa B (NF-κB) has been shown to drive the Aβ deposition, neuroinflammation and neurodegeneration in Alzheimer's disease (AD). Hence, selective targeting of activated p65 represents an attractive therapeutic approach for AD. Glucocorticoid induced leucine zipper (GILZ) is a NF-κB interactant that binds and sequesters the activated p65 in the cytoplasm. Read More

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Retinal Ganglion Cells Functional Changes in a Mouse Model of Alzheimer's Disease Are Linked with Neurotransmitter Alterations.

J Alzheimers Dis 2021 Mar 13. Epub 2021 Mar 13.

Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.

Background: Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. This neurodegenerative syndrome affects cognition, memory, behavior, and the visual system, particularly the retina.

Objective: This work aims to determine whether the 5xFAD mouse, a transgenic model of AD, displays changes in the function of retinal ganglion cells (RGCs) and if those alterations are correlated with changes in the expression of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters. Read More

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Accelerated long-term forgetting is a BACE1 inhibitor-reversible incipient cognitive phenotype in Alzheimer's disease model mice.

Masuo Ohno

Neuropsychopharmacol Rep 2021 Mar 22. Epub 2021 Mar 22.

Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA.

Aim: After the continued failure of β-secretase (BACE1) inhibitor clinical trials in prodromal as well as mild-to-moderate Alzheimer's disease (AD), they are shifting to further earlier or asymptomatic stages. The aim of this study is to explore a cognitive paradigm that allows us to more sensitively detect beneficial effects of BACE1 inhibitors in presymptomatic AD.

Methods: GRL-8234 (33. Read More

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