Neuropathology of Anti-Amyloid-β Immunotherapy: A Case Report

Rudolph J. Castellani, Elisheva D. Shanes, Matthew McCord, Nicholas J. Reish, Margaret Ellen Flanagan, M. Marsel Mesulam, Pouya Jamshidi

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Host responses to anti-amyloid-β (Aβ) antibody therapy are evident in neuroimaging changes and clinical symptoms in a subset of clinical trial subjects receiving such therapy. The pathological basis for the imaging changes and clinical symptoms is not known, nor is the precise mechanism of Aβ clearing. We report the autopsy findings in a 65-year-old woman who received three open label infusions of the experimental anti-Aβ drug lecanemab over about one month. Four days after the last infusion, she was treated with tissue plasminogen activator for acute stroke symptoms and died several days later with multifocal hemorrhage. Neuropathological examination demonstrated histiocytic vasculitis involving blood vessels with cerebral amyloid angiopathy. Fragmentation and phagocytosis of vascular Aβ were present throughout the cerebral cortex. Phagocytosis of parenchymal Aβ plaques was noted. Changes suggestive of Aβ and phosphorylated tau "clearing" were also noted. The findings overall suggest that anti-Aβ treatment stimulated a host response to Aβ, i.e., target engagement. The findings also provide evidence that amyloid-related imaging abnormalities might be indicative of an Aβ phagocytic syndrome within cerebral vasculature and parenchymal brain tissue in some cases.

Original languageEnglish (US)
Pages (from-to)803-813
Number of pages11
JournalJournal of Alzheimer's Disease
Volume93
Issue number2
DOIs
StatePublished - 2023

Keywords

  • Alzheimer’s disease
  • Apolipoprotein E
  • amyloid-related imaging abnormalities
  • amyloid-β
  • cerebral amyloid angiopathy
  • hemorrhage
  • lecanemab
  • phosphorylated tau
  • vasculitis

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Clinical Psychology
  • General Neuroscience

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