Alzheimer's disease: From immunotherapy to immunoprevention

Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4260 - 4270

Published: Sept. 1, 2023

Language: Английский

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The amyloid cascade hypothesis: an updated critical review

Brain, Journal Year: 2023, Volume and Issue: 146(10), P. 3969 - 3990

Published: May 15, 2023

Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer's disease have created excitement and been heralded as corroboration the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging biochemical data suggest a more complex aetiology. Here we review history weaknesses hypothesis in view new evidence obtained anti-amyloid antibodies. These indicate treatments either no or uncertain effect on cognition. Despite importance definition argue point playing minor aetiological role. We also discuss suggesting concerted activity many pathogenic factors propose evolving multi-factor models will better underpin search effective strategies treat disease.

Language: Английский

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Efficacy and safety of anti-amyloid-β monoclonal antibodies in current Alzheimer's disease phase III clinical trials: A systematic review and interactive web app-based meta-analysis

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 102012 - 102012

Published: July 7, 2023

Language: Английский

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Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy

Protein & Cell, Journal Year: 2024, Volume and Issue: unknown

Published: May 11, 2024

Abstract Alzheimer’s disease (AD), the leading cause of dementia, is characterized by accumulation amyloid plaques and neurofibrillary tangles in brain. This condition casts a significant shadow on global health due to its complex multifactorial nature. In addition genetic predispositions, development AD influenced myriad risk factors, including aging, systemic inflammation, chronic conditions, lifestyle, environmental exposures. Recent advancements understanding pathophysiology are paving way for enhanced diagnostic techniques, improved assessment, potentially effective prevention strategies. These discoveries crucial quest unravel complexities AD, offering beacon hope management treatment options millions affected this debilitating disease.

Language: Английский

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Lecanemab for early Alzheimer's disease: Appropriate use recommendations from the French federation of memory clinics

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100094 - 100094

Published: Feb. 1, 2025

Language: Английский

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Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer’s disease

Brain Communications, Journal Year: 2023, Volume and Issue: 5(3)

Published: Jan. 1, 2023

Abstract The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment Alzheimer’s disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At time writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food Drug Administration accelerated approval, further agents this in pipeline. Based limited published trial data date, regulators, payors physicians will need assess efficacy, effectiveness safety, as well cost accessibility. We propose that attention three important questions related safety should guide evidence-based consideration drugs. These are: (1) Were statistical analyses appropriate did they convincingly support claims efficacy? (2) Do reported effects outweigh concerns are generalizable representative population people disease? (3) demonstrate modification, suggesting increasing benefits beyond duration trials likely? suggest specific approaches interpreting results these highlight areas uncertainty where additional cautious interpretation existing warranted. Safe, effective accessible treatments eagerly awaited millions patients caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying treatments, rigorous unbiased assessment critical regulatory decision-making subsequently determining provision utility routine practice. Our recommendations provide framework appraisal payors, patients.

Language: Английский

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Impacts of FDA approval and Medicare restriction on antiamyloid therapies for Alzheimer's disease: patient outcomes, healthcare costs, and drug development

The Lancet Regional Health - Americas, Journal Year: 2023, Volume and Issue: 20, P. 100467 - 100467

Published: March 1, 2023

In 2021, the US Food and Drug Administration (FDA) granted approval to aducanumab, an antiamyloid antibody for early-stage Alzheimer's disease, despite a lack of clear clinical evidence demonstrating drug's cognitive benefits. The manufacturer initially priced drug at staggering $56,000 per year, price that was later reduced $28,200. Unfortunately, these costs do not include additional expenses associated with monitoring treatment. However, Centers Medicare Medicaid Services (CMS) recently announced they will only cover individuals enrolled in trials limit coverage future antibodies. This discrepancy between FDA CMS positions has caused confusion concerns patients who could potentially benefit from therapy. It is important acknowledge economic uncertainties surrounding aducanumab its potential impacts on development processes. FDA's approval, limited evidence, raises questions about integrity rigor process. high cost also accessibility concerns, especially those without insurance or sufficient financial resources. Given CMS's policy, it's critical evaluate long-term implications this decision development. Without adequate support providers, treatments may be hindered. summary, pricing coupled created confusing concerning landscape patients. It's stakeholders, including patients, clinicians, insurers, regulatory bodies, work together address challenges ensure have access effective, affordable treatments.

Language: Английский

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Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(2), P. 1284 - 1297

Published: Nov. 20, 2023

Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.

Language: Английский

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The effectiveness and value of lecanemab for early Alzheimer disease: A summary from the Institute for Clinical and Economic Review’s California Technology Assessment Forum

Journal of Managed Care & Specialty Pharmacy, Journal Year: 2023, Volume and Issue: 29(9), P. 1078 - 1083

Published: Aug. 23, 2023

Language: Английский

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Mesenchymal and Neural Stem Cell-Derived Exosomes in Treating Alzheimer’s Disease

Bioengineering, Journal Year: 2023, Volume and Issue: 10(2), P. 253 - 253

Published: Feb. 15, 2023

As the most common form of dementia and a progressive neurodegenerative disorder, Alzheimer’s disease (AD) affects over 10% world population with age 65 older. The is neuropathologically associated loss neurons synapses in specific brain regions, deposition amyloid plaques neurofibrillary tangles, neuroinflammation, blood–brain barrier (BBB) breakdown, mitochondrial dysfunction, oxidative stress. Despite intensive effort, there still no cure for disorder. Stem cell-derived exosomes hold great promise treating various diseases, including AD, as they contain variety anti-apoptotic, anti-inflammatory, antioxidant components. Moreover, stem also promote neurogenesis angiogenesis can repair damaged BBB. In this review, we will first outline major neuropathological features AD; subsequently, discussion cells, cell-secreted exosomes, exosome isolation methods follow. We then summarize recent data involving use mesenchymal cell- or neural AD. Finally, briefly discuss challenges, perspectives, clinical trials using AD therapy.

Language: Английский

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