Amyloid-related imaging abnormalities associated with immunotherapy in Alzheimer's disease patients. (July 2012)

• Record Type: Journal Article
• Authors: Panza, Francesco; Frisardi, Vincenza; Imbimbo, Bruno P; Logroscino, Giancarlo; Seripa, Davide; Pilotto, Alberto; Solfrizzi, Vincenzo
• Is Part Of: Future neurology. Volume 7:Number 4(2012)
• Page Start: 395
• Page End: 401
• Publication Date: 2012-07
• Subjects: Alzheimer's disease -- amyloid-β -- amyloid-related imaging abnormalities -- bapineuzumab -- passive immunotherapy; Neurology -- Research -- Periodicals; 611.8005
• DOI: 10.2217/fnl.12.42
• Languages: English
• ISSNs: 1479-6708

Abstract

Evaluation of: Sperling R, Salloway S, Brooks DJ et al. Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 11(3), 241–249 (2012). 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/T2 * 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 ε 4 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.