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Alzheimer's disease outlook: controversies and future directions

Frisoni, Giovanni B; Aho, Emil; Brayne, Carol; Ciccarelli, Olga; Dubois, Bruno; Fox, Nick C; Frederiksen, Kristian S; ... Hansson, Oskar; + view all (2025) Alzheimer's disease outlook: controversies and future directions. The Lancet , 406 (10510) pp. 1424-1442. 10.1016/S0140-6736(25)01389-3. Green open access

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Abstract

For the first time, reductions in cerebral β-amyloid pathology load and rate of cognitive and functional decline have been achieved in Alzheimer's disease, through pharmacological intervention in randomised controlled trials. However, the results from phase 3 randomised controlled trials of anti-β amyloid monoclonal antibodies are interpreted in different ways, with some experts supporting a clinically meaningful disease-modifying effect, and others judging insufficient benefit-to-risk ratio and opposing market authorisation. In the final paper of this Series, we discuss these contrasting views, all of which wish to contribute to improvements in the quality of life of people with, or at risk of, Alzheimer's disease. We contrast the efficacy, societal costs, and generalisability of monoclonal antibodies for Alzheimer's disease to biologics for other conditions (eg, cancer, multiple sclerosis, and rheumatoid arthritis) and set this debate in the larger context of modern personalised medicine. We discuss current practice implications, future developments directed to β-amyloid and non-amyloid targets that might have more clinical efficacy and less adverse effects for those with the disease, and large-scale prevention interventions for those at risk.

Type: Article
Title: Alzheimer's disease outlook: controversies and future directions
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/S0140-6736(25)01389-3
Publisher version: https://doi.org/10.1016/s0140-6736(25)01389-3
Language: English
Additional information: This is an open access article distributed under the terms of the Creative Commons CC-BY license, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10216551
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