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The Alzheimer’s therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia

Lecanemab, a leading therapy for Alzheimer’s disease, induces an Fc-mediated transcriptional program in human microglia, linked to osteopontin and enhanced plaque phagocytosis, suggesting alternative strategies to promote plaque clearance.

Giulia Albertini
Magdalena Zielonka
Bart De Strooper
ResearchOpen Access24 Nov 2025
Nature Neuroscience

Volume: 29, P: 100-110
The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia xenografted into a mouse model of Alzheimer’s disease

APOE is the strongest risk gene for late onset Alzheimer’s disease and its expression is upregulated in microglia in response to amyloid beta. Here, the authors show that the APOE isoforms show different transcriptomic and epigenomic responses to amyloid, by studying human microglia transplanted into the brain of an Alzheimer’s disease mouse model.

Kitty B. Murphy
Di Hu
Sarah J. Marzi
ResearchOpen Access27 May 2025
Nature Communications

Volume: 16, P: 1-15
Xenografted human microglia display diverse transcriptomic states in response to Alzheimer’s disease-related amyloid-β pathology

Human microglia transplanted in the mouse brain mount a multipronged response to amyloid-β pathology, displaying unique transcriptional states. Alzheimer’s disease risk genes are differentially regulated across cell states and profoundly alter microglial function.

Renzo Mancuso
Nicola Fattorelli
Bart De Strooper
ResearchOpen Access27 Mar 2024
Nature Neuroscience

Volume: 27, P: 886-900
Stem-cell-derived human microglia transplanted in mouse brain to study human disease

Human stem cell-derived microglia integrate into mouse brain, displaying transcriptome signatures of microglia directly isolated from human brain and providing a chimeric model to study human-specific aspects of Alzheimer’s disease and other brain diseases.

Renzo Mancuso
Johanna Van Den Daele
Bart De Strooper
Research28 Oct 2019
Nature Neuroscience

Volume: 22, P: 2111-2116
Stem-cell-derived human microglia transplanted into mouse brain to study human disease

Mancuso and De Strooper and colleagues describe MIGRATE (microglia in vitro generation refined for advanced transplantation experiments, a combined in vitro differentiation and in vivo xenotransplantation protocol for studying human microglia transplanted into mouse brain.

Nicola Fattorelli
Anna Martinez-Muriana
Renzo Mancuso
Protocols11 Jan 2021
Nature Protocols

Volume: 16, P: 1013-1033

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The Alzheimer’s therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia

The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia xenografted into a mouse model of Alzheimer’s disease

Xenografted human microglia display diverse transcriptomic states in response to Alzheimer’s disease-related amyloid-β pathology

Stem-cell-derived human microglia transplanted in mouse brain to study human disease

Stem-cell-derived human microglia transplanted into mouse brain to study human disease

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