期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 93, 期 2, 页码 803-813出版社
IOS PRESS
DOI: 10.3233/JAD-221305
关键词
Alzheimer's disease; amyloid-beta; amyloid-related imaging abnormalities; Apolipoprotein E; cerebral amyloid angiopathy; hemorrhage; lecanemab; phosphorylated tau; vasculitis
A 65-year-old woman who received three infusions of an experimental anti-A beta drug showed neuroimaging changes and clinical symptoms. Autopsy findings revealed histiocytic vasculitis, fragmentation and phagocytosis of vascular A beta, and clearance of A beta and phosphorylated tau. These findings suggest that anti-A beta treatment led to a host response and indicate the presence of an A beta phagocytic syndrome within cerebral vasculature and brain tissue.
Host responses to anti-amyloid-beta (A beta) 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 A beta clearing. We report the autopsy findings in a 65-year-old woman who received three open label infusions of the experimental anti-A beta 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 A beta were present throughout the cerebral cortex. Phagocytosis of parenchymal A beta plaques was noted. Changes suggestive of A beta and phosphorylated tau clearing were also noted. The findings overall suggest that anti-A beta treatment stimulated a host response to A beta, i.e., target engagement. The findings also provide evidence that amyloid-related imaging abnormalities might be indicative of an A beta phagocytic syndrome within cerebral vasculature and parenchymal brain tissue in some cases.
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