The authors should cite the literature on CSF levels of amyloid-β (total and 1-42). Without having a comparison and seeing a discussion of previous CSF studies, I do not know whether the reduced level in CSF is good, bad, or a chance event. Antibodies to amyloid-β could opsonize amyloid-β deposits for phagocytosis by macrophages, which are probably the critical cells for phagocytosis of amyloid-β deposits in human brain (Fiala et al., submitted for publication).

View all comments by Milan Fiala

This pilot study by Dodel et al. demonstrates the effect of passive immunization in Alzheimer’s patients with the intravenous immunoglobulin prepared from the plasma pools of normal, healthy donors, based on the fact that healthy individuals have circulating auto-antibodies against Aβ peptide.

They found that the immunization performed in five patients reduced CSF Aβ, while the levels of serum Aβ were increased. There was no significant change found in Aβ42 levels. Given the fact that Aβ42 is a pathogenic “seeding” peptide, it is interesting as to how unchanged levels of Aβ42 following passive immunization would be effective. The authors themselves speculate “whether the observed reduction may have an impact on plaque formation”! This might be the explanation why MMSE scores were not affected after the treatment.

Secondly, the observed increase in the levels of serum Aβ is highly likely to trigger vasculopathy and microhemorrhage.

Thirdly, this study has been performed only in five patients. Out of these, one patient was excluded since he refused to get a lumbar...  Read more

This pilot study by Dodel et al. demonstrates the effect of passive immunization in Alzheimer’s patients with the intravenous immunoglobulin prepared from the plasma pools of normal, healthy donors, based on the fact that healthy individuals have circulating auto-antibodies against Aβ peptide.

They found that the immunization performed in five patients reduced CSF Aβ, while the levels of serum Aβ were increased. There was no significant change found in Aβ42 levels. Given the fact that Aβ42 is a pathogenic “seeding” peptide, it is interesting as to how unchanged levels of Aβ42 following passive immunization would be effective. The authors themselves speculate “whether the observed reduction may have an impact on plaque formation”! This might be the explanation why MMSE scores were not affected after the treatment.

Secondly, the observed increase in the levels of serum Aβ is highly likely to trigger vasculopathy and microhemorrhage.

Thirdly, this study has been performed only in five patients. Out of these, one patient was excluded since he refused to get a lumbar puncture. As the authors themselves suggest, “this study requires detailed clinical assessment.”

In summary, although this study provides an additional proof for pursuing immunization in treating AD, it is inconclusive.

The inconclusiveness of this study could be due to:

1. Very small sample size;
2. Unchanged levels of a key pathogenic Aβ42;
3. Unchanged MMSE scores;
4. Projected risk of vasculopathy and hemorrhage due to elevated serum Aβ levels.

View all comments by Neelima Chauhan

I think that this is an interesting paper, and new for the future. The study in this paper was not blinded, had no group with placebo, and the groups were too small. I think that the authors of the paper should continue their study using intravenous immunoglobulins in the treatment of Alzheimer disease. The authors are changing the method of investigating Alzheimer disease.

View all comments by Ryszard Pluta