Evidence map›Paper›PMID 37649100›Full record

ArticleMolecular neurodegeneration2023

Amyloid-β (Aβ) immunotherapy induced microhemorrhages are associated with activated perivascular macrophages and peripheral monocyte recruitment in Alzheimer's disease mice.

Xavier Taylor, Isaiah M Clark, Griffin J Fitzgerald, Herold Oluoch, Justin T Hole, Ronald B DeMattos, Yaming Wang, Feng Pan

Open access · goldAbstract read
In one paragraph

Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
14.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 80 citations in OpenAlex.

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  17. The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Xavier TaylorNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Isaiah M ClarkNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Griffin J FitzgeraldNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Herold OluochNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Justin T HoleNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Ronald B DeMattosNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA. demattos_ronald_bradley@lilly.com.ORCID http://orcid.org/0009-0008-7651-1807
Yaming WangNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Feng PanNeuroscience Discovery, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
Eli Lilly (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAmyloid-related imaging abnormalities (ARIA) have been identified as the most common and serious adverse events resulting from pathological changes in the cerebral vasculature during several recent anti-amyloid-β (Aβ) immunotherapy trials. However, the precise cellular and molecular mechanisms underlying how amyloid immunotherapy enhances cerebral amyloid angiopathy (CAA)-mediated alterations in vascular permeability and microhemorrhages are not currently understood. Interestingly, brain perivascular macrophages have been implicated in regulating CAA deposition and cerebrovascular function however, further investigations are required to understand how perivascular macrophages play a role in enhancing CAA-related vascular permeability and microhemorrhages associated with amyloid immunotherapy.

methodsIn this study, we examined immune responses induced by amyloid-targeting antibodies and CAA-induced microhemorrhages using histology and gene expression analyses in Alzheimer's disease (AD) mouse models and primary culture systems.

resultsIn the present study, we demonstrate that anti-Aβ (3D6) immunotherapy leads to the formation of an antibody immune complex with vascular amyloid deposits and induces the activation of CD169

conclusionsIn summary, our study establishes a connection between Aβ antibodies engaged at CAA deposits, the activation of perivascular macrophages, and the upregulation of genes involved in vascular permeability. However, the implications of this phenomenon on the susceptibility to microhemorrhages remain to be fully elucidated. Further investigations are warranted to determine the precise role of CD169 + perivascular macrophages in enhancing CAA-mediated vascular permeability, extravasation of plasma proteins, and infiltration of immune cells associated with microhemorrhages.

Indexed as

Alzheimer DiseaseCerebral Amyloid AngiopathyAmyloid beta-PeptidesAmyloidogenic ProteinsAnimalsMacrophagesMiceMonocytesPlaque, AmyloidAmyloid beta-PeptidesAmyloidogenic Proteins

Identifiers

PMID37649100
PMCPMC10469415
OpenAlexW4386284835

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.