Case Report Suggests Alternative Role for Anti-Amyloid Antibodies
Although noone knows exactly why vasogenic brain edema occurs in patients* treated with anti-amyloid antibodies (like Pfizer/JNJ’s bapineuzumab and possibly Lilly’s solanezumab), the speculation is that the antibodies attack amyloid deposits surrounding cerebral blood vessels—thus causing fluid leakage from the cerebral vasculature. Support for the idea is now available in a case study in the most recent issue of Neurology.
Italian investigators report the case of a 68-year-old man with cerebral amyloid angiopathy (CAA) who developed autoantibodies (detected in CSF) against beta amyloid proteins 1-40 and 1-42. Autoantibody titers, importantly, paralleled the rise and fall of clinical and radiographic signs of vasogenic edema.
In an accompanying editorial (“Life Imitates Art“), Greenberg and Frosch of Harvard are intrigued but advise caution. The Italian case was not confirmed pathologically, they note, and, in their experience, the identification of autoantibodies in other cases of CAA has been elusive. They speculate, nevertheless, that therapeutic anti-amyloid antibodies, despite their apparently significant limitations in the treatment of Alzheimer disease, may have, on the basis of this report, some role in the management of CAA.
CSF = cerebrospinal fluid.
* About 10% in the bapineuzumab phase 2 trial (Salloway S et al. Neurology. 2009;73:2061–2070).
Photograph of atrophied brain from person with AD: National Institute on Alcohol Abuse and Alcoholism.