Impact of Anti-amyloid-β Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer’s Disease: A Focus on Aducanumab and Lecanemab

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: April 12, 2022

Alzheimer's disease (AD) is the most prevalent form of age-related dementia in world, and its main pathological features consist amyloid-β (Aβ) plaque deposits neurofibrillary tangles formed by hyperphosphorylated tau protein. So far, only a few AD treatments approved have been applied clinic, but effects these drugs are limited for partial symptomatic relief to patients with unable alter progression. Later, all efforts targeting pathogenic factors were unsuccessful over past decades, which suggested that pathogenesis complex. Recently, disease-modifying therapies (DMTs) can change underlying pathophysiology AD, anti-Aβ monoclonal antibodies (mabs) (e.g., aducanumab, bapineuzumab, gantenerumab, solanezumab, lecanemab) developed successively conducted clinical trials based on theory systemic failure cell-mediated Aβ clearance contributes occurrence In review, we summarized recent studies therapeutic trial results mabs AD. Specifically, focused discussion impact aducanumab lecanemab pathology profiles. The review provides possible evidence applying immunotherapy analyzes lessons learned from order further study adverse

Language: Английский

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Aducanumab: evidence from clinical trial data and controversies

Drugs in Context, Journal Year: 2021, Volume and Issue: 10, P. 1 - 9

Published: Sept. 30, 2021

Alzheimer's disease (AD) is the most common cause for dementia worldwide. Until recently, all approved treatments AD were symptomatic and not modifying. On 7 June 2021, US FDA aducanumab, a human IgG1 anti-Aβ monoclonal antibody selective Aβ aggregates, as first disease-modifying treatment AD. Aducanumab in United States of mild cognitive impairment or mild-dementia stage In this Editorial, we review trial data aducanumab controversies that its approval has generated.

Language: Английский

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Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg?

Antioxidants, Journal Year: 2021, Volume and Issue: 10(9), P. 1479 - 1479

Published: Sept. 16, 2021

The pathogenesis of Alzheimer's disease involves β amyloid (Aβ) accumulation known to induce synaptic dysfunction and neurodegeneration. brain's vulnerability oxidative stress (OS) is considered a crucial detrimental factor in disease. OS Aβ are linked each other because induces OS, increases the deposition. Thus, answer question "which comes first: chicken or egg?" remains extremely difficult. In any case, evidence for primary occurrence AD attractive. indicates that long period gradual damage precedes results appearance clinical pathological symptoms, including deposition, neurofibrillary tangle formation, metabolic dysfunction, cognitive decline. Moreover, plays role many risk factors AD. begins years before its antioxidant treatment can be an important therapeutic target attacking

Language: Английский

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Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(6), P. 1117 - 1117

Published: May 24, 2022

Alzheimer’s disease (AD) is the most common cause of dementia. The pathophysiology this characterized by accumulation amyloid-β, leading to formation senile plaques, and intracellular presence neurofibrillary tangles based on hyperphosphorylated tau protein. In therapeutic approach AD, we can identify three important fronts: approved drugs currently available for treatment disease, which include aducanumab, donepezil, galantamine, rivastigmine, memantine, a combination memantine donepezil; therapies under investigation that work mainly Aβ pathology pathology, γ-secretase inhibitors, β-secretase α-secretase modulators, aggregation metal interfering drugs, enhance clearance, inhibitors protein hyperphosphorylation, promote clearance tau, finally, other alternative designed improve lifestyle, thus contributing prevention disease. Therefore, aim review was analyze describe current treatments possible future alternatives in AD.

Language: Английский

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Amyloid-Related Imaging Abnormalities With Anti-amyloid Antibodies for the Treatment of Dementia Due to Alzheimer's Disease

Frontiers in Neurology, Journal Year: 2022, Volume and Issue: 13

Published: March 23, 2022

Second-generation anti-amyloid monoclonal antibodies are emerging as a viable therapeutic option for individuals with prodromal and mild dementia due to Alzheimer's disease (AD). Passive immunotherapy aducanumab (Aduhelm), lecanemab, donanemab, gantenerumab all lower CNS amyloid (Aβ) burden but come significant risk of amyloid-related imaging abnormality (ARIA)—the most common side effect this class drugs. While usually asymptomatic detected only on brain MRI, ARIA may lead new signs symptoms including headache, worsening confusion, dizziness, visual disturbances, nausea, seizures. In addition, one fatality related ARIA-E (edema) ARIA-H (hemorrhage) donanemab reported date. be associated excessive neuroinflammation saturation perivascular clearance pathways, while vascular weakening rupture small blood vessels. The is higher at treatment initiation, in ApoE4 carriers, dosage, >4 microhemorrhages baseline MRI. increases age cerebrovascular disease. Dose titration mitigates the ARIA, contraindications include those prescribed anti-platelet or anti-coagulant A MRI required before initiated, each scheduled dose escalation, any neurologic sign symptom. Management ranges from continued antibody monthly monitoring temporary permanent suspension symptomatic moderate severe Controlled studies regarding prevention lacking, anecdotal evidence suggests that pulse intravenous corticosteroids benefit, well course anticonvulsant

Language: Английский

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Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US

JAMA Neurology, Journal Year: 2022, Volume and Issue: 79(5), P. 478 - 478

Published: March 28, 2022

Several anti-amyloid monoclonal antibodies have been developed for slowing the progression of Alzheimer disease (AD). Among furthest are aducanumab, which received accelerated approval from US Food and Drug Administration in 2021, donanemab, is currently undergoing phase 3 trials. The cost-effectiveness these treatments has not established.

Language: Английский

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Puerarin: a potential natural neuroprotective agent for neurological disorders

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114581 - 114581

Published: March 24, 2023

Puerarin is an isoflavone compound derived from Pueraria lobata in traditional Chinese medicine. Accumulating evidence has indicated that puerarin demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Based on the latest research progress as a neuroprotective agent, its activity, molecular mechanism, therapeutic application were systematically reviewed with emphasis pre-clinical studies. The related information was extracted compiled major scientific databases, including PubMed, ScienceDirect, SpringerLink, National Knowledge Infrastructure, using 'Puerarin', 'Neuroprotection', 'Apoptosis', 'Autophagy', 'Antioxidant', 'Mitochondria', 'Anti-inflammation' keywords. This review complied Preferred Reporting Items Systematic Reviews criteria. Forty-three articles met established inclusion exclusion shown against variety of disorders, ischemic cerebrovascular disease, subarachnoid hemorrhage, epilepsy, cognitive traumatic brain injury, Parkinson's Alzheimer's anxiety, depression, diabetic neuropathy, neuroblastoma/glioblastoma. anti-apoptosis, proinflammatory mediator inhibitory, autophagy regulatory, anti-oxidative stress, mitochondria protection, Ca2+ influx anti-neurodegenerative activities. exerts noticeable models disorders vivo (animal). will contribute to development novel clinical drug candidate However, well-designed, high-quality, large-scale, multicenter randomized studies are needed determine safety utility patients

Language: Английский

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The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Language: Английский

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Alzheimer’s disease and its treatment–yesterday, today, and tomorrow

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 24, 2024

Alois Alzheimer described the first patient with Alzheimer’s disease (AD) in 1907 and today AD is most frequently diagnosed of dementias. a multi-factorial neurodegenerative disorder familial, life style comorbidity influences impacting global population more than 47 million projected escalation by 2050 to exceed 130 million. In USA demographic encompasses approximately six individuals, expected increase surpass 13 2050, antecedent phase AD, recognized as mild cognitive impairment (MCI), involves nearly 12 individuals. The economic outlay for management AD-related decline estimated at 355 billion USD. addition, intensifying prevalence cases countries modest intermediate income further enhances urgency therapeutically cost-effective treatments improving quality patients their families. This narrative review evaluates pathophysiological basis an initial focus on therapeutic efficacy limitations existing drugs that provide symptomatic relief: acetylcholinesterase inhibitors (AChEI) donepezil, galantamine, rivastigmine, N-methyl-D-aspartate receptor (NMDA) allosteric modulator, memantine. hypothesis amyloid-β (Aβ) tau are appropriate targets have potential halt progress critically analyzed particular clinical trial data anti-Aβ monoclonal antibodies (MABs), namely, aducanumab, lecanemab donanemab. challenges dogma targeting Aβ will benefit majority subjects MABs unlikely be “magic bullet”. A comparison benefits disadvantages different classes forms determining new directions research alternative drug undergoing pre-clinical assessments. we discuss stress importance treatment co-morbidities, including hypertension, diabetes, obesity depression known risk developing AD.

Language: Английский

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Aducanumab, a Novel Anti-Amyloid Monoclonal Antibody, for the Treatment of Alzheimer’s Disease: A Comprehensive Review

Health psychology research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Jan. 30, 2022

Alzheimer’s disease (AD) is the most common form of dementia affecting millions individuals, including family members who often take on role as caregiver. This debilitating reportedly consumes 8% total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors N-methyl-D-aspartate receptor antagonists have historically been widely used pharmacologic therapies patients AD, however, these drugs are not curative. review discusses epidemiology, pathophysiology, risk factors, presentation, current treatment AD followed by novel monoclonal antibody, aducanumab, in AD. Currently aducanumab only Food Drug Administration (FDA) approved drug that acts to slow progression this disease. Aducanumab anti-amyloid which functions selectively binding amyloid aggregates both oligomeric fibrillar states. Studies show may help restore neurological function reducing beta-amyloid plaques reestablishing neuronal calcium permeability. However, there concern magnitude drug’s benefit be statistically significant clinically significant. Despite skepticism, has proven significantly decrease all cortical brain regions examined. In summary, provided hope those working toward goal providing a safe viable option management

Language: Английский

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