Journal Article

DZNE-2023-00178

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Anti-amyloid antibody therapies in Alzheimer's disease.

Perneczky, R. (First author)DZNE* ; Jessen, F.DZNE* ; Grimmer, T. ; Levin, J.DZNE* ; Flöel, A.Extern* ; Peters, O.DZNE* ; Froelich, L.

2023
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awad005

Abstract: After years of failed attempts to develop a disease-modifying therapy for Alzheimer's disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-β protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-β lowering on PET also underpin the positive results of the trial. In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer's disease failed. We compare the safety profiles of the different antibodies and highlight cautionary measures for their routine clinical use. Last, we discuss the role of blood-based biomarkers in transforming the clinical care pathway to facilitate the uptake of antibody treatments, proposing an integrated case-finding and treatment model crossing the different healthcare sectors. Taken together, a real breakthrough may have been achieved by proving that amyloid-β reduction results in clinical benefits, rather than just biomarker changes. At the same time, routine use of the new generation of drugs will show if statistical efficacy translates into clinically meaningful change. This may just be the beginning of a new era of Alzheimer's disease drug development.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Amyloid (MeSH) ; Treatment Outcome (MeSH) ; Antibodies, Monoclonal (MeSH) ; Biomarkers (MeSH) ; Cognitive Dysfunction: metabolism (MeSH) ; Disease Progression (MeSH) ; anti-amyloid immunization ; anti-amyloid immunisation ; disease progression ; fluid and imaging biomarkers ; mild cognitive impairment and dementia ; monoclonal antibodies ; treatment of cognitive decline ; Amyloid beta-Peptides ; Amyloid ; Antibodies, Monoclonal ; Biomarkers

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Contributing Institute(s):

1. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
2. Clinical Alzheimer’s Disease Research (AG Jessen)
3. Clinical Neurodegeneration (AG Levin)
4. Vascular Pathology (AG Dirnagl)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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