Passive amyloid-β immunotherapy in Alzheimer’s disease : a multicellular clearance system beyond plaque removal
Zhan, Xiaoni LU ; Liu, Chenchen LU ; Yu, Changjiang ; Lindblom, Nils LU ; Deierborg, Tomas LU
; Kobro-Flatmoen, Asgeir
; Gouras, Gunnar K.
LU
and Wen, Gehua
LU
(2026)
In Molecular Neurodegeneration
21.
- Abstract
Passive immunotherapy targeting amyloid-β (Aβ) has emerged as a major therapeutic strategy for Alzheimer’s disease (AD), yet its clinical benefits remain modest and are frequently accompanied by vascular adverse events such as amyloid-related imaging abnormalities (ARIA). While the removal of extracellular Aβ plaques is associated with therapeutic efficacy, accumulating evidence suggests that additional cellular and vascular mechanisms may also contribute to complementary therapeutic outcomes alongside plaque removal. Recent studies show that Aβ antibodies are broadly distributed within the brain and interact with multiple neural and immune cell populations, rather than being limited to Aβ plaques. These observations support an expanded... (More)
Passive immunotherapy targeting amyloid-β (Aβ) has emerged as a major therapeutic strategy for Alzheimer’s disease (AD), yet its clinical benefits remain modest and are frequently accompanied by vascular adverse events such as amyloid-related imaging abnormalities (ARIA). While the removal of extracellular Aβ plaques is associated with therapeutic efficacy, accumulating evidence suggests that additional cellular and vascular mechanisms may also contribute to complementary therapeutic outcomes alongside plaque removal. Recent studies show that Aβ antibodies are broadly distributed within the brain and interact with multiple neural and immune cell populations, rather than being limited to Aβ plaques. These observations support an expanded view of passive Aβ immunotherapy as a multicellular coordinated clearance process. Aβ antibodies engage diverse cellular and anatomical compartments, including neurons, glial cells, perivascular macrophages, peripheral immune cells, and meningeal lymphatic pathways, thereby influencing Aβ dynamics across intracellular and extracellular pools. Within this framework, therapeutic outcomes are influenced not only by plaque clearance but also by interactions between Aβ antibodies and cellular and anatomical compartments that regulate Aβ clearance and treatment-associated vascular response. This perspective may help explain variability in clinical efficacy and the emergence of vascular side effects, while also providing additional considerations for optimizing Aβ antibody design and therapeutic strategies.
(Less)
- author
- Zhan, Xiaoni
LU
; Liu, Chenchen
LU
; Yu, Changjiang
; Lindblom, Nils
LU
; Deierborg, Tomas
LU
; Kobro-Flatmoen, Asgeir
; Gouras, Gunnar K.
LU
and Wen, Gehua
LU
- organization
- publishing date
- 2026-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, Amyloid-related imaging abnormalities (ARIA), Amyloid-β immunotherapy, Cell-type-specific-interactions, Multicellular clearance network
- in
- Molecular Neurodegeneration
- volume
- 21
- article number
- 37
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:105044838003
- pmid:42464289
- ISSN
- 1750-1326
- DOI
- 10.1186/s13024-026-00972-y
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2026.
- id
- 2f7ad3e6-5eb9-4e54-aec8-1fefac332bdb
- date added to LUP
- 2026-07-29 13:50:14
- date last changed
- 2026-07-31 03:24:18
@article{2f7ad3e6-5eb9-4e54-aec8-1fefac332bdb,
abstract = {{<p>Passive immunotherapy targeting amyloid-β (Aβ) has emerged as a major therapeutic strategy for Alzheimer’s disease (AD), yet its clinical benefits remain modest and are frequently accompanied by vascular adverse events such as amyloid-related imaging abnormalities (ARIA). While the removal of extracellular Aβ plaques is associated with therapeutic efficacy, accumulating evidence suggests that additional cellular and vascular mechanisms may also contribute to complementary therapeutic outcomes alongside plaque removal. Recent studies show that Aβ antibodies are broadly distributed within the brain and interact with multiple neural and immune cell populations, rather than being limited to Aβ plaques. These observations support an expanded view of passive Aβ immunotherapy as a multicellular coordinated clearance process. Aβ antibodies engage diverse cellular and anatomical compartments, including neurons, glial cells, perivascular macrophages, peripheral immune cells, and meningeal lymphatic pathways, thereby influencing Aβ dynamics across intracellular and extracellular pools. Within this framework, therapeutic outcomes are influenced not only by plaque clearance but also by interactions between Aβ antibodies and cellular and anatomical compartments that regulate Aβ clearance and treatment-associated vascular response. This perspective may help explain variability in clinical efficacy and the emergence of vascular side effects, while also providing additional considerations for optimizing Aβ antibody design and therapeutic strategies.</p>}},
author = {{Zhan, Xiaoni and Liu, Chenchen and Yu, Changjiang and Lindblom, Nils and Deierborg, Tomas and Kobro-Flatmoen, Asgeir and Gouras, Gunnar K. and Wen, Gehua}},
issn = {{1750-1326}},
keywords = {{Alzheimer's disease; Amyloid-related imaging abnormalities (ARIA); Amyloid-β immunotherapy; Cell-type-specific-interactions; Multicellular clearance network}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{Molecular Neurodegeneration}},
title = {{Passive amyloid-β immunotherapy in Alzheimer’s disease : a multicellular clearance system beyond plaque removal}},
url = {{http://dx.doi.org/10.1186/s13024-026-00972-y}},
doi = {{10.1186/s13024-026-00972-y}},
volume = {{21}},
year = {{2026}},
}