• ChAT-inhibition kinetics
• Choline acetyltransferase (ChAT)
• In vitro screening
• Molecular dynamics (MD)
• Positron emission tomography (PET)
• Structure-based virtual screening

• Choline O-Acetyltransferase/metabolism
• Choline O-Acetyltransferase/antagonists & inhibitors
• Choline O-Acetyltransferase/chemistry
• Humans
• Ligands
• Furans/chemistry
• Furans/pharmacology
• Furans/metabolism
• Molecular Dynamics Simulation
• Drug Discovery
• Pyridones/chemistry
• Pyridones/pharmacology
• Pyridones/metabolism
• Molecular Docking Simulation
• Enzyme Inhibitors/pharmacology
• Enzyme Inhibitors/chemistry
• Enzyme Inhibitors/metabolism
• Structure-Activity Relationship
• Animals

• Protein Multimerization
• Amyloid beta-Peptides/chemistry
• Amyloid beta-Peptides/metabolism
• Metal Nanoparticles/chemistry
• Silver/chemistry
• Drug Evaluation, Preclinical/methods
• Electrochemical Techniques/methods
• Proteolysis/drug effects

• Aging pathways
• Alzheimer’s Disease
• DeepDrug
• Directed biomedical graph
• Expert-led AI drug-repurposing
• Graph neural network
• Immunological
• Inflammation
• Lead combination of AD drugs
• Long genes
• Neuro-degenerative
• Pathway convergence
• Somatic and germline mutations

• Alzheimer Disease/drug therapy
• Drug Repositioning/methods
• Humans
• Artificial Intelligence
• Drug Combinations
• Drug Therapy, Combination

• US National Academy of Medicine (NAM) Healthy Longevity Catalyst Award 2021
• “An Artificial Intelligence (AI)-driven Causal Approach for Early Diagnosis and Treatment of Late Onset Alzheimer’s Disease” under Seed Fund for Collaborative Research, The University of Hong Kong

• AD treatments
• Engineered activated neutrophil exosomes
• Mitochondrial health
• Mitophagy
• Multi-target therapy

• Alzheimer’s disease
• Huntington’s disease
• Parkinson’s disease
• alcohol-use disorders
• cannabinoid receptors
• endocannabinoids
• epilepsy
• neurodegenerative disorders
• psychiatric disorders
• substance-use disorders

• Humans
• Cannabis/chemistry
• Animals
• Cannabinoids/pharmacology
• Cannabinoids/chemistry
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/chemistry
• Neuroprotective Agents/therapeutic use
• Nervous System Diseases/drug therapy
• Nervous System Diseases/metabolism
• Cannabidiol/pharmacology
• Cannabidiol/chemistry
• Cannabidiol/therapeutic use
• Blood-Brain Barrier/metabolism
• Blood-Brain Barrier/drug effects
• Dronabinol/pharmacology
• Dronabinol/chemistry

• AA029686 NIH HHS

• Alzheimer’s Disease
• HDAC
• Multi-Target Drug

• Alzheimer Disease/drug therapy
• Humans
• Histone Deacetylase Inhibitors/chemistry
• Histone Deacetylase Inhibitors/pharmacology
• Histone Deacetylase Inhibitors/chemical synthesis
• Histone Deacetylase Inhibitors/therapeutic use
• Histone Deacetylases/metabolism
• Drug Design
• Molecular Structure
• Animals
• Structure-Activity Relationship

• Alzheimer’s disease
• amyloid-β degradation
• ascorbate oxidase
• ceruloplasmin

• Amyloid beta-Peptides/metabolism
• Animals
• Humans
• Oxidoreductases/metabolism
• Neurons/metabolism
• Induced Pluripotent Stem Cells/metabolism
• Mice

• Alzheimer’s disease
• Bapineuzumab
• confidence interval (CI)
• risk ratio (RR).
• safety
• vasogenic edema

• Humans
• Alzheimer Disease/drug therapy
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized/adverse effects
• Edema/chemically induced

• Alzheimer’s disease
• Amyloid beta
• Donor-π-acceptor
• Fluorescence
• Indane

• Mice
• Animals
• Alzheimer Disease/diagnostic imaging
• Alzheimer Disease/metabolism
• Fluorescent Dyes/chemistry
• Protein Aggregates
• Molecular Docking Simulation
• Amyloid beta-Peptides/metabolism
• Mice, Transgenic
• Brain/metabolism
• Plaque, Amyloid/chemistry
• Plaque, Amyloid/diagnosis
• Plaque, Amyloid/pathology

• Alzheimer's disease
• Network pharmacology
• Neuroinflammation
• Oxidative stress
• Paeoniflorin

• R01 AG055413 NIA NIH HHS
• R21 AG059134 NIA NIH HHS
• S10 OD028609 NIH HHS

• Alzheimer’s disease
• blood–brain barrier
• cell membrane biomimetic nanoparticles
• targeting peptides

• Cognition
• Guanosine monophosphate
• Guanylyl cyclase
• Pharmacokinetics
• Spatial memory

Alzheimer’s disease (AD) as a neurodegenerative disease occupies 3/5–4/5 cases among patients with dementia, yet its pathogenetic mechanism remains unclear. Geraniol, on the other hand, is a well-known extract from essential oils of aromatic plants and has been proven that it has outstanding neuroprotective effects as well as ameliorating influence in memory impairment. Therefore, the present study aims to elucidate the potential of geraniol against AD by network pharmacology-based approach combined with molecular modeling study.

Firstly, we evaluated the druggability of geraniol by ADME method. Then, we obtained the geraniol targets and AD-related targets from multiple open data sources. Afterward, we calculated the intersection through a Venn diagram to find common targets, and via Panther classification system to categorize them. In order to gain a macroscopic understanding of these common targets, we carried out GO terms and KEGG pathways enrichment analyses, according to which we constructed a compound–target–pathway–disease network. In addition, we built a preliminary PPI network which was further analyzed both functionally and topologically. Consequently, five hub targets were sorted out. Finally, we conducted molecular docking and molecular dynamic simulation to validate our findings.

In the present study, the pharmacological properties of geraniol were assessed according to ADME and Lipinski’s rule, which demonstrate promising druggability. Then, from 10,972 AD-related targets and 33 geraniol targets, 29 common targets were identified, among which 38.1% of them are metabolite interconversion enzymes, 23.8% are protein modifying enzymes, 33.3% are transmembrane receptors, and the rest are transporters. Enrichment analyses hint that geraniol is involved in cholinergic synapse, serotonergic synapse, and neuroactive ligand–receptor interaction. We also built a preliminary PPI network to investigate the interplay between these targets and their extensive interactions. Then, by functionally clustering the preliminary PPI network, we gained a cluster of proteins which formed a subnetwork with score of 8.476, and 22 nodes. Its results of GO terms and KEGG pathways enrichment analyses once again suggests that geraniol actively participates in cholinergic synapse, serotonergic synapse, and neuroactive ligand–receptor interaction, which are believed to be strongly associated with AD pathogenesis. Besides, topological analyses of the preliminary PPI network helped find 5 hub targets (i.e., CHRM3, PRKCA, PRKCD, JAK1, JAK2). To verify their interaction with geraniol molecule, we conducted molecular docking, and found that CHRM3 possesses the highest affinity in binding, indicating that geraniol molecules are closely bound to each hub target, and CHRM3 may serve as a key target of geraniol against AD. It was then further confirmed by molecular dynamic simulation, the result of which supports our hypothesis.

The present study shares a mechanistic insight of the potential of geraniol against AD, giving a reference to future experimental studies.

The online version contains supplementary material available at 10.1186/s40001-022-00699-8.

• Alzheimer’s disease
• Data integration
• Drug discovery
• Geraniol
• Network modeling

• Alzheimer’s disease (AD)
• acetylcholinesterase (AChE)
• molecular docking
• molecular dynamins
• natural compounds
• virtual screening

• Acetylcholinesterase/chemistry
• Alzheimer Disease/drug therapy
• Antioxidants/pharmacology
• Antioxidants/therapeutic use
• Cholinesterase Inhibitors/chemistry
• Galantamine/pharmacology
• Humans
• Molecular Docking Simulation

• D-78/2018 Council on Medical Science at the Medical University of Sofia
• BG05M2OP001-1.001-0003 Science and Education for Smart Growth Operational Program (2014-2020)
• . D01-271/2019 Bulgarian National Roadmap for Research Infrastructure (2017-2023)

Presently, there is a lack of effective disease-modifying drugs for the treatment of Alzheimer’s disease (AD). Uncaria rhynchophylla (UR) and its predominant active phytochemicals alkaloids have been studied to treat AD. This study used a novel network pharmacology strategy to identify UR alkaloids against AD from the perspective of AD pathophysiological processes and identified the key alkaloids for specific pathological process. The analysis identified 10 alkaloids from UR based on high-performance liquid chromatography (HPLC) that corresponded to 127 targets correlated with amyloid-β (Aβ) pathology, tau pathology and Alzheimer disease pathway. Based on the number of targets correlated with AD pathophysiological processes, angustoline, angustidine, corynoxine and isocorynoxeine are highly likely to become key phytochemicals in AD treatment. Among the 127 targets, JUN, STAT3, MAPK3, CCND1, MMP2, MAPK8, GSK3B, JAK3, LCK, CCR5, CDK5 and GRIN2B were identified as core targets. Based on the pathological process of AD, angustoline, angustidine and isocorynoxeine were identified as the key UR alkaloids regulating Aβ production and corynoxine, isocorynoxeine, dihydrocorynatheine, isorhynchophylline and hirsutine were identified as key alkaloids that regulate tau phosphorylation. The findings of this study contribute to a more comprehensive understanding of the key alkaloids and mechanisms of UR in the treatment of AD, as well as provide candidate compounds for drug research and development for specific AD pathological processes.

• National Natural Science Foundation of China

Alzheimer’s disease (AD) is the most common reason for progressive dementia in the elderly. It has been shown that disorders of the mammalian/mechanistic target of rapamycin (mTOR) signaling pathways are related to the AD. On the other hand, diabetes mellitus (DM) is a risk factor for the cognitive dysfunction. The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate, which contains neuro-inflammation and/or neurodegeneration and dementia. Glucagon-like peptide-1 (GLP1) is interesting as a possible link between metabolism and brain impairment. Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD. The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit. They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes. Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4 (DPP4) inhibitors, being currently used for DM therapy, may also be effective for AD treatment. The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models. Although further studies for mTOR, GLP1, and DPP4 signaling pathways in humans would be intensively required, they seem to be a promising approach for innovative AD-treatments. We would like to review the characteristics of AD pathogenesis, the key roles of mTOR in AD and the preventive and/ or therapeutic suggestions of directing the mTOR signaling pathway.

• Alzheimer’s disease
• Cognitive disorder
• Dementia
• Glucagon-like peptide-1
• Dipeptidyl peptidase-4
• Mammalian/mechanistic target of rapamycin

• Alzheimer's disease
• herbal bio actives
• macrophages
• medicinal plants
• microglial
• monocytes
• novel drug delivery

• Alzheimer’s disease
• Neuroprotectin D1
• autophagy
• glycogen synthase kinase 3

• ADMET analysis
• Acetylcholinesterase
• Butyrylcholinesterse
• Molecular docking
• Tinosporide

• AD pathology
• Alzheimer’s disease
• Uncaria rhynchophylla
• alkaloids
• network pharmacology

• Alzheimer's disease
• mechanism
• network pharmacology
• resveratrol

• Alzheimer Disease/drug therapy
• Alzheimer Disease/genetics
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Humans
• Molecular Docking Simulation
• Phosphatidylinositol 3-Kinases
• Resveratrol/pharmacology

• drug screening
• biomedical engineering
• nanoparticles

• Amyloid/chemistry
• Amyloid beta-Peptides/chemistry
• Gold/chemistry
• Kinetics
• Ligands
• Metal Nanoparticles/chemistry
• Metal Nanoparticles/ultrastructure
• Protein Aggregates
• Time Factors

• National Research Foundation of Korea (NRF)

The effect of Alzheimer’s disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. CD4+ T cells could both exacerbate and reduce AD symptoms based on their infiltrating subpopulations. Proinflammatory subpopulations such as Th1 and Th17 constitute a major source of proinflammatory cytokines that reduce endothelial integrity and stimulate astrocytes, resulting in the production of amyloid β. Anti-inflammatory subpopulations such as Th2 and Tregs reduce inflammation and regulate the function of Th1 and Th17. Recently, pathogenic Th17 has been shown to have a superior infiltrating capacity compared to other major CD4+ T cell subpopulations. Alzheimer’s drugs such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda) are known to play an important part in regulating the mechanisms of the neurotransmitters. However, little is known about the effect of these drugs on CD4+ T cell subpopulations’ infiltration of the brain during AD. In this review, we focus on understanding the influence of AD drugs on CD4+ T cell subpopulation interactions with the BBB in AD. While current AD therapies improve endothelial integrity and reduce astrocytes activations, they vary according to their influence on various CD4+ T cell subpopulations. Donepezil reduces the numbers of Th1 but not Th2, Rivastigmine inhibits Th1 and Th17 but not Th2, and memantine reduces Th1 but not Treg. However, none of the current AD drugs is specifically designed to target the dysregulated balance in the Th17/Treg axis. Future drug design approaches should specifically consider inhibiting CD4+ Th17 to improve AD prognosis.

• Alzheimer
• CD4+ T cells
• Th17
• blood brain barrier
• migration

• Alzheimer’s disease
• clinical trial
• granular tau oligomer
• inhibitor
• methylene blue
• oligomer
• protein aggregation
• tau protein

• Molecular modelling
• drug discovery
• formulation and development
• molecular docking
• molecular modeling
• pharmaceutical research.

• Acetylcholinesterase inhibitors
• Alzheimer's disease
• Disease modifying therapy
• Pathophysiology

• ABCB1
• Blood–brain barrier
• Donepezil
• P-glycoprotein (P-gp)
• abcb1ab knock-out mice

Alzheimer’s disease (AD) is a multifactorial disorder characterized by exponential loss of memory and cognitive deficit involving several disease modifying targets (amyloid beta, beta-secretase, monoaminoxidase-B, and cholinesterase). The present study explores multi-target directed ligand approach using secondary metabolite reserpine (RES) and ajmalicine (AJM) obtained from Rauwolfia serpentina roots. Novel LCMS and HPLC methods were developed for identification and quantification of reserpine and ajmalicine. In vitro enzyme inhibition assays were performed to evaluate anti-cholinesterase, β-site amyloid cleaving enzyme (BACE-1) inhibition and monoamine oxidase-B (MAO-B) inhibition, further analyzed with in silico analysis. Anti-amyloidogenic potential was studied using anti-aggregation studies along with TEM and circular dichroism (CD) analysis. In vitro neuroprotective potential against Aβ toxicity and anti-oxidative stress was demonstrated using PC12 cell cultures. Reserpine is a more potent dual cholinesterase inhibitor than ajmalicine (IC₅₀ values of 1.7 μM (AChE) and 2.8 μM (BuChE)). The anti-aggregation activity of reserpine (68%) was more than ajmalicine (56%). Both compounds demonstrated neuroprotective activity against Aβ42 (92%) and H₂O₂ (93%) induced toxicity in PC12 cells against controls. Phytocompounds also inhibited MAO-B and BACE-1 enzymes in concentration dependent manner. Molecular docking studies indicated the strong binding of compounds to the catalytic site of targets. This novel study demonstrated that reserpine and ajmalicine as a multi-target directed ligand that have disease modifying potential for amelioration of AD.

• Alzheimer’s disease
• Aβ
• BACE-1
• MAO-B
• ajmalicine
• molecular docking
• multi target directed ligand
• rauwolfia serpentina
• reserpine

• Alzheimer’s disease
• Ang(1–7)/Mas receptor system
• angiotensin II/AT1 receptor system
• angiotensin IV/AT4 receptor system
• insulin-regulated aminopeptidase (IRAP)
• renin-angiotensin system (RAS)

A rigidification strategy was applied to the preclinical candidate donecopride, an acetylcholinesterase inhibitor possessing 5-HT₄R agonist activity. Inspired by promising bioactive benzisoxazole compounds, we have conducted a pharmacomodulation study to generate a novel series of multitarget directed ligands. The chemical synthesis of the ligand was optimized and compounds were evaluated in vitro against each target and in cellulo. Structure-activity relationship was supported by docking analysis in human acetylcholinesterase binding site. Among the synthesized compounds, we have identified a novel hybrid 32a (3-[2-[1-(cyclohexylmethyl)-4-piperidyl]ethyl]-4-methoxy-1,2-benzoxazole) able to display nanomolar acetylcholinesterase inhibitory effects and nanomolar Ki for 5-HT₄R.

Alzheimer’s disease (AD) is a neurodegenerative disorder mostly influencing the elderly, and causes death due to dementia. The main pathogenic feature connected with the progression of this multifactorial disease is the weakening of the cholinergic system in the brain. Cholinesterase (ChE) inhibitors are recognized as one of the choices in the treatment of AD. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were approved as a therapeutic strategy to reduce the symptoms of AD and prevent its progression. The capacity of BChE is not completely known yet; rather, it is accepted to assume a part in a few disorders such as AD. Thus, BChE inhibitors may have a greater role for the treatment of AD in the future. In the present study, 2-(9-acridinylamino)-2-oxoethyl piperazine/piperidine/morpholinecarbodithioate derivatives were synthesized in order to investigate anticholinesterase activity. Eight derivatives demonstrated a specific and promising action against BChE. Furthermore, compound 4n showed inhibitory activity against both enzymes. It was found that the active compounds were well tolerated in the cytotoxicity test. Possible interactions between the lead compound, 4n, and the BChE enzyme were determined through a docking study. The findings obtained within this paper will contribute to the development of new and effective synthetic anti-Alzheimer compounds, and will ideally encourage future screening against AD.

• 9-aminoacridine
• Alzheimer’s disease
• acetylcholinesterase
• butyrylcholinesterase
• dithiocarbamate salts
• docking study

• Acetylcholinesterase/chemistry
• Acetylcholinesterase/metabolism
• Alzheimer Disease/drug therapy
• Animals
• Blood-Brain Barrier/drug effects
• Blood-Brain Barrier/metabolism
• Butyrylcholinesterase/chemistry
• Butyrylcholinesterase/metabolism
• Cell Line
• Cell Survival/drug effects
• Chemistry Techniques, Synthetic
• Cholinesterase Inhibitors/chemical synthesis
• Cholinesterase Inhibitors/chemistry
• Cholinesterase Inhibitors/pharmacology
• Enzyme Activation/drug effects
• Humans
• Kinetics
• Mice
• Molecular Conformation
• Molecular Docking Simulation
• Molecular Dynamics Simulation
• Protein Binding
• Structure-Activity Relationship

• Acetylcholinesterase
• Alzheimer’s disease
• pharmacophore
• shape filter
• virtual screening

Extensive epidemiological and clinical studies revealed that Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (T2D) are most likely to appear simultaneously in aged people as T2D is a major risk factor for AD. Therefore, development of potential multifunctional agents for dual therapy of AD and T2D has received much attention. Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis have been used extensively in popular medicine. The present study was aimed at phytochemical profiling and evaluating multifunctional ability of titled plants in the AD and T2D dual therapy.

Methanolic extracts and their derived fractions were evaluated for their inhibitory capacities against acetylcholinesterase (AChE) & butyrylcholinesterase (BuChE), and α– & β–glucosidase besides kinetic analysis of inhibition using methods of Elmann and Shibano, respectively. Antioxidant potency of active fractions was assessed by their DPPH and ABTS radical scavenging activities. Active fractions were tested by the MTT assay to verify cytotoxicity and neuroprotective ability in human nueroblastoma cell lines. Phytochemical screening was done with the aid of spectrophotometric methods.

All the methanolic extracts of test plants (BAM, HIM, RMM) showed concentration dependent inhibitory activities against AChE, BuChE, α– and β–glucosidase enzymes. Subsequent fractionation and evaluation revealed that chloroform fractions BAC, HIC and RMC with IC₅₀ values of 12.29±2.14, 9.94±2.14, 16.65±1.99 and 27.38±1.24; 28.14±0.9, 5.16±0.22, 11.03±0.5 and 87.64±15.41; 41.35±1.6, 15.86±7.3, 26.04±0.37 and 25.33±0.3 were most prominent with regard to inhibition potential against AChE, BuChE, α– and β–glucosidase, respectively. Kinetic analysis of these active fractions proved that they disclosed mixed-type inhibition against AChE, BuChE, α– and β–glucosidase enzymes. In the MTT assay, active fractions BAC, HIC, RMC showed significant cell viability at high concentrations (400 μg). Moreover, in MTT assay, the active fractions displayed excellent neuroprotective effects against oxidative stress induced cell death and significant cell viability in SK N SH cells at all concentrations.

The strong anticholinesterase, antiglucosidase, antioxidant and neuroprotective activities of methanolic extracts and their derived chloroform fractions indicate the potential of Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis as multifunctional therapeutic remedies for the dual therapy of T2D and AD.

The online version of this article (10.1186/s12906-018-2140-x) contains supplementary material, which is available to authorized users.

• Anticholinesterase activity
• Antidiabetic activity
• Antioxidant activity
• Buchanania axillaris
• Hemidesmus indicus
• Phytochemical profile
• Rhus mysorensis

• alkaloids
• berberine
• diabetes
• immune system
• inflammation
• insulin
• neurodegeneration

• Alzheimer’s disease
• Huntington’s disease
• Parkinson’s disease
• alpha synuclein
• beta amyloid
• huntingtin
• nonhuman primates

• Amyloid beta-Peptides/metabolism
• Animals
• Animals, Genetically Modified
• Disease Models, Animal
• Haplorhini
• Humans
• Huntingtin Protein/metabolism
• Neurodegenerative Diseases/metabolism
• Neurodegenerative Diseases/pathology
• Parkinson Disease/metabolism
• Parkinson Disease/pathology
• Primates

• P51 OD011106 NIH HHS
• R24 OD019803 NIH HHS
• UL1 TR000427 NCATS NIH HHS

Aging is a risk factor for a number of “age-related diseases”, including Alzheimer’s disease (AD). AD affects more than a third of all people over the age of 85, and is the leading cause of dementia worldwide. Symptoms include forgetfulness, memory loss, and cognitive decline, ultimately resulting in the need for full-time care. While there is no cure for AD, pharmacological approaches to alleviate symptoms and target underlying causes of the disease have been developed, albeit with limited success. This review presents the age-related, genetic, and environmental risk factors for AD and proposes a hypothesis for the mechanistic link between genetics and the environment. In short, much is known about the genetics of early-onset familial AD (EO-FAD) and the central role played by the Aβ peptide and protein misfolding, but late-onset AD (LOAD) is not thought to have direct genetic causes. Nonetheless, genetic risk factors such as isoforms of the protein ApoE have been identified. Additional findings suggest that air pollution caused by the combustion of fossil fuels may be an important environmental risk factor for AD. A hypothesis suggesting that poor air quality might act by disrupting protein folding homeostasis (proteostasis) is presented.

• Alzheimer’s disease
• ApoE
• air pollution
• amyloid beta
• particulate matter

• Alzheimer′s disease
• MTDL
• antioxidants
• pyrrolizinones
• β-amyloid

In brains of Alzheimer’s disease (AD), reactive oxygen species (ROS) levels are significantly higher than that of healthy brains. Evidence suggests that, during AD onset and progression, a vicious cycle revolves around amyloid beta (Aβ) production, aggregation, plaque formation, microglia/immunological responses, inflammation, and ROS production. In this cycle, ROS species play a central role, and H₂O₂ is one of the most important ROS species. In this report, we have designed a fluorescent imaging probe CRANAD-88, which is capable of cascade amplifying near infrared fluorescence (NIRF) signals at three levels upon interacting with H₂O₂ in AD brains. We demonstrated that the amplification was feasible in vitro and in vivo. Remarkably, we showed that, for the first time, it was feasible to monitor the changes of H₂O₂ concentrations in AD brains before and after treatment with an H₂O₂ scavenger. Our method opens new revenues to investigate H₂O₂ in AD brains and can be very instructive for drug development.

• Alzheimer’s disease
• Benzazepine derivatives
• Excitotoxicity
• NMDAR

• Acetylcholine iodide
• Acetylcholinesterase
• Alzheimer’s disease
• Competitive inhibition
• Glimepiride
• Type 2 Diabetes Mellitus

• Alzheimer Disease/drug therapy
• Alzheimer Disease/metabolism
• Cholinesterase Inhibitors/chemistry
• Cholinesterase Inhibitors/metabolism
• Cholinesterase Inhibitors/therapeutic use
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• Humans
• Hypoglycemic Agents/chemistry
• Hypoglycemic Agents/metabolism
• Hypoglycemic Agents/therapeutic use
• Molecular Docking Simulation/methods
• Sulfonylurea Compounds/chemistry
• Sulfonylurea Compounds/metabolism
• Sulfonylurea Compounds/therapeutic use