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Myeloid-mediated cerebral amyloid vasculitis and the potential role of the immune response in brain atrophy
Rudy J. Castellani, Hinda Najem, Amy B. Heimberger, Pouya Jamshidi
Rudy J. Castellani, Hinda Najem, Amy B. Heimberger, Pouya Jamshidi
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Research Letter Immunology Neuroscience Vascular biology

Myeloid-mediated cerebral amyloid vasculitis and the potential role of the immune response in brain atrophy

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Abstract

Authors

Rudy J. Castellani, Hinda Najem, Amy B. Heimberger, Pouya Jamshidi

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Figure 1

Spatial proteomic multiplex immunofluorescence analysis comparing a lecanemab-treated case with an untreated Alzheimer’s disease case.

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Spatial proteomic multiplex immunofluorescence analysis comparing a leca...
(A) Multiplex images showing differences in cortical vessel wall and immune infiltration between cases. CD31 was used to indicate endothelial cells; ACTA2 was used to indicate smooth muscle; CD11c was used to indicate antigen-presenting cells; P2RY12 was used to indicate microglia; LAMP1 was used to indicate activated myeloid cells; Rab5 was used to indicate phagocytosis. Aβ, amyloid β. Scale bars: 100 μm (top); 50 μm (bottom). (B) Multiplex images showing CD11c+ APCs infiltrating the cortical vessel wall with cytoplasmic Aβ (red arrows). Scale bar: 50 μm. (C) Multiplex images in the lecanemab-treated case (left), showing fibrinogen and fibronectin within cortical vessels along with hemorrhage. Scale bar: 200 μm. Remnants of the vessel wall and Aβ amyloid within CD11c+ APCs (red arrow) are shown (right). Scale bar: 50 μm. (D and E) Representative images of spleen from the lecanemab-treated or untreated case showing expression of Aβ, GFAP, or MBP within CD68+ monocytes. Scale bars: 20 μm. Of note, Aβ+ macrophages were present in the lecanemab-treated and untreated Alzheimer’s disease spleen (~60%), while GFAP+ and MBP+ splenic macrophages were noted only in the lecanemab-treated spleen (42% and 20%, respectively).

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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