Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?
The amyloid cascade hypothesis for Alzheimer’s disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis’ claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have b...
| Main Authors: | , , , , , , |
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| Format: | Article |
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MDPI AG
2024
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| Online Access: | https://hdl.handle.net/1721.1/154127 |
| _version_ | 1811072324518019072 |
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| author | Høilund-Carlsen, Poul F. Alavi, Abass Castellani, Rudolph J. Neve, Rachael L. Perry, George Revheim, Mona-Elisabeth Barrio, Jorge R. |
| author_facet | Høilund-Carlsen, Poul F. Alavi, Abass Castellani, Rudolph J. Neve, Rachael L. Perry, George Revheim, Mona-Elisabeth Barrio, Jorge R. |
| author_sort | Høilund-Carlsen, Poul F. |
| collection | MIT |
| description | The amyloid cascade hypothesis for Alzheimer’s disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis’ claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer’s antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain. |
| first_indexed | 2024-09-23T09:04:11Z |
| format | Article |
| id | mit-1721.1/154127 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:04:11Z |
| publishDate | 2024 |
| publisher | MDPI AG |
| record_format | dspace |
| spelling | mit-1721.1/1541272024-04-28T05:02:39Z Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? Høilund-Carlsen, Poul F. Alavi, Abass Castellani, Rudolph J. Neve, Rachael L. Perry, George Revheim, Mona-Elisabeth Barrio, Jorge R. Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis The amyloid cascade hypothesis for Alzheimer’s disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis’ claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer’s antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain. 2024-04-12T14:17:02Z 2024-04-12T14:17:02Z 2024-03-31 2024-04-12T13:14:25Z Article http://purl.org/eprint/type/JournalArticle 1422-0067 https://hdl.handle.net/1721.1/154127 Høilund-Carlsen PF, Alavi A, Castellani RJ, Neve RL, Perry G, Revheim M-E, Barrio JR. Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? International Journal of Molecular Sciences. 2024; 25(7):3892. PUBLISHER_CC 10.3390/ijms25073892 International Journal of Molecular Sciecnes Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG Multidisciplinary Digital Publishing Institute |
| spellingShingle | Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis Høilund-Carlsen, Poul F. Alavi, Abass Castellani, Rudolph J. Neve, Rachael L. Perry, George Revheim, Mona-Elisabeth Barrio, Jorge R. Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? |
| title | Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? |
| title_full | Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? |
| title_fullStr | Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? |
| title_full_unstemmed | Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? |
| title_short | Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers? |
| title_sort | alzheimer s amyloid hypothesis and antibody therapy melting glaciers |
| topic | Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| url | https://hdl.handle.net/1721.1/154127 |
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