Article
Radiology, Nuclear Medicine & Medical Imaging
Heidi R. R. Wassef, Patrick M. M. Colletti
Summary: Hoilund-Carlsen and colleagues express concerns about the reliability of amyloid PET for excluding Alzheimer's disease. We provide additional studies on amyloid PET and discuss the diagnostic challenges in Alzheimer's disease. We also discuss the limitations of amyloid in the diagnosis and evaluation of therapy response in AD.
CLINICAL NUCLEAR MEDICINE
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Heidi R. Wassef, Patrick M. Colletti
Summary: This article discusses important issues related to amyloid PET, diagnosis of Alzheimer's disease, and the recently approved antiamyloid treatment aducanumab. It also explores new developments that may guide us towards methods of presymptomatic detection of Alzheimer's disease and the development of effective prevention and therapy.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Clinical Neurology
Edward D. Plowey, Thierry Bussiere, Raj Rajagovindan, Jennifer Sebalusky, Stefan Hamann, Christian von Hehn, Carmen Castrillo-Viguera, Alfred Sandrock, Samantha Budd Haeberlein, Christopher H. van Dyck, Anita Huttner
Summary: This article reports the first autopsy of a patient with Alzheimer's disease (AD) who was previously treated with Aducanumab. The findings show that Aducanumab can reduce A beta plaque neuropathology, but has a lesser effect on pTau neuropathology. This case report underscores the importance of autopsy neuropathology studies in understanding the mechanism of action and impact of Aducanumab on AD biomarkers.
ACTA NEUROPATHOLOGICA
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Poul F. Hoilund-Carlsen, Thomas J. Werner, Abass Alavi, Mona-Elisabeth Revheim
Summary: When the FDA granted accelerated approval for Biogen's Alzheimer disease drug Aduhelm, they deviated from their mission of ensuring drug safety and efficacy. The approval was solely based on a perceived reduction in brain amyloid deposits, without considering its proven clinical effect. We believe that the amyloid-PET scans, which indicate decreasing amyloid deposits, actually reflect increased cerebral cell death caused by aducanumab treatment. Consequently, we can expect a worsening, rather than an improvement, in the condition of treated patients over time.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Clinical Neurology
Lukas Sveikata, Andreas Charidimou, Anand Viswanathan
Summary: This article reviews the implications of aducanumab amyloid-beta immunotherapy for treating Alzheimer's disease with comorbid cerebral amyloid angiopathy. It discusses the potential impact of cerebral amyloid angiopathy on the effectiveness of immunotherapy and proposes strategies to identify it in patients considered for this treatment.
Article
Clinical Neurology
Winston Chiong, Benjamin David Tolchin, Richard J. Bonnie, Katharina M. Busl, Salvador Cruz-Flores, Leon G. Epstein, Ericka P. Greene, Judy Illes, Matthew Kirschen, Daniel G. Larriviere, Sneha Mantri, Michael A. Rubin, Barney J. Stern, Lynne P. Taylor
Summary: Alzheimer's disease is a feared and stigmatized condition that has a significant impact on patients, families, and society as a whole. There is an urgent need for further research in effective treatments for AD, and patients require more support from clinicians and communities, with trust being a fundamental aspect of this support.
Review
Biochemistry & Molecular Biology
Karolina Wojtunik-Kulesza, Monika Rudkowska, Anna Orzel-Sajdlowska
Summary: In June 2021, the FDA approved a new drug for Alzheimer's disease called Aducanumab. This monoclonal antibody IgG1 targets amyloid beta, a main cause of Alzheimer's disease. Clinical trials have shown that Aducanumab can reduce amyloid beta and improve cognition. However, there is controversy surrounding its limitations, costs, and side effects. This review focuses on the mechanism of action of Aducanumab and discusses both the positive and negative aspects of the therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Gerhard Leinenga, Wee Kiat Koh, Juergen Goetz
Summary: The study found that both Adu and SUS reduced the total plaque area in the hippocampus, with no additional effect observed with the combination treatment. In the cortex, only the combination treatment yielded a significant decrease in total plaque area compared to sham. The SUS and SUS + Adu groups were able to significantly reduce plaque load in some animals to below 1% from above 10%. The group receiving the combination treatment showed a robust improvement in spatial memory, and Adu levels were five times higher in this group compared to those receiving Adu alone.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Review
Medicine, Research & Experimental
Tapan Behl, Ishnoor Kaur, Aayush Sehgal, Sukhbir Singh, Neelam Sharma, Hafiz A. Makeen, Mohammed Albratty, Hassan A. Alhazmi, Shatha Ghazi Felemban, Amal M. Alsubayiel, Saurabh Bhatia, Simona Bungau
Summary: The article discusses the discovery of aducanumab as an antibody-based immunotherapy for Alzheimer's disease and the controversies surrounding its FDA approval. It explores the failure of anti-amyloid therapies in AD and the impact of aducanumab in AD models, as well as its potential implications.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Serena Silvestro, Andrea Valeri, Emanuela Mazzon
Summary: Alzheimer's disease is a neurodegenerative disorder with beta-amyloid plaques and neurofibrillary tangles of Tau proteins as its main pathological mechanisms. Aducanumab, a monoclonal antibody targeting A beta, has shown promising results in reducing Aβ accumulation and slowing cognitive impairment progression, potentially marking a milestone in the development of efficient drugs for AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
C. Mallinckrodt, Y. Tian, P. S. Aisen, F. Barkhof, S. Cohen, G. Dent, O. Hansson, K. Harrison, T. Iwatsubo, C. J. Mummery, K. K. Muralidharan, I. Nestorov, L. Nisenbaum, R. Rajagovindan, C. von Hehn, C. H. van Dyck, B. Vellas, S. Wu, Y. Zhu, A. Sandrock, T. Chen, S. Budd Haeberlein
Summary: Post-hoc analyses of the EMERGE and ENGAGE studies showed that the outcomes in the high-dose group of ENGAGE were affected by an imbalance in a small number of rapidly progressing patients and lower exposure to the target dose. However, these factors were only present in early enrolled patients and did not affect later enrolled patients. Baseline characteristics and amyloid-related imaging abnormalities did not contribute to the difference in results between the high-dose arms.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Article
Multidisciplinary Sciences
Kathleen M. Schoch, Lubov A. Ezerskiy, Michaela M. Morhaus, Riley N. Bannon, Andrew D. Sauerbeck, Mark Shabsovich, Paymaan Jafar-nejad, Frank Rigo, Timothy M. Miller
Summary: The study found that transient reduction of Trem2 messenger RNA levels in APP/PS1 mice significantly reduced plaque deposition and attenuated microglial association around plaques. The results suggest that Trem2 reduction may activate microglia and aid in plaque removal.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
S. Budd Haeberlein, P. S. Aisen, F. Barkhof, S. Chalkias, T. Chen, S. Cohen, G. Dent, O. Hansson, K. Harrison, C. von Hehn, T. Iwatsubo, C. Mallinckrodt, C. J. Mummery, K. K. Muralidharan, I. Nestorov, L. Nisenbaum, R. Rajagovindan, L. Skordos, Y. Tian, C. H. van Dyck, B. Vellas, S. Wu, Y. Zhu, A. Sandrock
Summary: Aducanumab showed significant changes in early Alzheimer's disease patients in one trial, but did not meet primary or secondary endpoints in another study. Both trials demonstrated a dose- and time-dependent reduction in pathophysiological markers of Alzheimer's disease.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)
Article
Chemistry, Multidisciplinary
Qianhua Feng, Ning Wang, Xueli Zhang, Yuying Mei, Rongkun Fu, Jing Chen, Xiaomin Yuan, Shuaiqi Yang, Zhenzhong Zhang, Hongjuan Zhao, Lei Wang
Summary: A nanoparticle cluster is designed to prevent amyloid fibrillation by binding to amyloid-beta through a multivalent binding strategy. The cluster decomposes into smaller nanoparticles upon reaching the Alzheimer's disease nidus, which bind strongly to amyloid-beta and disrupt amyloid interactions. The resulting nanoparticle-amyloid composite delivers rapamycin to microglia, improving the immune dysfunction and removing amyloid-beta, ultimately rescuing memory deficits in Alzheimer's disease.
Article
Clinical Neurology
J. Cummings, G. D. Rabinovici, A. Atri, P. Aisen, L. G. Apostolova, S. Hendrix, M. Sabbagh, D. Selkoe, M. Weiner, S. Salloway
Summary: Aducanumab (Aduhelm) has been approved in the United States for the treatment of patients with mild cognitive impairment or mild dementia due to Alzheimer's disease. The update of the appropriate use recommendations (AURs) aims to refine the guidelines based on real-world use and provide better patient selection, decision-making, safety monitoring, and risk mitigation. The importance of detecting past medical conditions and performing APOE genotyping to prevent complications and improve detection of amyloid-related imaging abnormalities (ARIA) is emphasized. MRI is suggested for better monitoring, and additional parameters for treatment discontinuation are proposed considering recurrent or serious ARIA. This update does not address efficacy, price, or insurance coverage, and serves as a guide for clinicians.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)