Abstract
Amyloid-related imaging abnormalities (ARIAs) have been reported in patients with Alzheimer's disease treated with bapineuzumab, a monoclonal antibody targeting β-amyloid (Aβ). The spectrum of ARIA includes signal hyperintensities on fluid attenuation inversion recovery sequences thought to represent 'vasogenic edema' and/or sulcal effusion (ARIA-E), as well as signal hypointensities on gradient echo/T 2* thought to represent hemosiderin deposits. This study was a retrospective analysis in which two neuroradiologists independently reviewed 2572 fluid attenuation inversion recovery MRI scans from 262 participants in two Phase II studies of bapineuzumab and an open-label extension study. In this analysis, several ARIA-E cases were identified that were initially missed in the reported studies of bapineuzumab (42%). Associated clinical symptoms were observed in only 22% of patients with ARIA-E. Occurrence of ARIA-E increased with bapineuzumab dose and presence of apolipoprotein E (APOE) ε4 alleles. The increased risk of ARIA-E in APOE ε4 carriers and the knowledge that vasogenic edema and microhemorrhages may spontaneously occur in cerebral amyloid angiopathy suggest a potential relationship with vascular Aβ burden. The increased risk of ARIA with a high bapineuzumab dose and the findings from a case with PET amyloid imaging also suggest a possible relationship between ARIA-E with Aβ clearance after passive immunotherapy with monoclonal antibodies.
Original language | English |
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Pages (from-to) | 395-401 |
Number of pages | 7 |
Journal | Future Neurology |
Volume | 7 |
Issue number | 4 |
DOIs | |
Publication status | Published - Jul 2012 |
Keywords
- Alzheimer's disease
- amyloid-β
- amyloid-related imaging abnormalities
- bapineuzumab
- passive immunotherapy
ASJC Scopus subject areas
- Neurology
- Clinical Neurology