The idea that immunization against amyloid-β (Aβ) could be an effective therapy against Alzheimer's disease (AD) suffered a significant setback earlier this year after reports of inflammatory reactions in patients that took part in an initial clinical trial. Although the cause of the inflammation remains unknown, this observation prompted many critics to argue that the days of immunization as a possible AD therapy were over. But as two recent papers from the laboratories of David Holtzman and Steven Paul show, we still have a lot to learn from the use of anti-Aβ antibodies, which might compel us to reconsider their diagnostic and therapeutic potential.

In the first paper, DeMattos et al. measured the plasma concentration of Aβ before and after the administration of an anti-Aβ antibody to transgenic mice that expressed a human form of the amyloid precursor protein, and tried to correlate this with the brain amyloid burden (an index of the amount of Aβ that is present in the brain). As is the case in people with AD, the authors found no correlation between the basal plasma levels of Aβ and brain amyloid burden. However, the plasma concentration of Aβ increased 24 hours after a single antibody injection, and there was a strong correlation between the new level of Aβ and brain amyloid burden. In other words, plasma levels of Aβ after the injection were predictive of the brain amyloid burden. As the brain accumulation of Aβ in people with AD precedes the onset of cognitive impairments and neuronal loss, this approach could lead to the development of a diagnostic tool for people at risk.

In the second paper, Dodart et al. found that a similar acute administration of the antibody reduced the memory deficits that had previously been reported in the transgenic mice, without altering the brain amyloid burden. As they detected Aβ/antibody complexes in the plasma and cerebrospinal fluid of the mice, the authors propose that the memory improvements might be due to sequestration of soluble Aβ from the brain.

Although we can only speculate on the implications of these findings for patients with Alzheimer's disease, both studies converge on the idea that the clearance of Aβ from the brain is a dynamic process, and that the use of anti-Aβ antibodies provide us with a useful window through which we can examine this phenomenon.