Longitudinal effects of intravenous immunoglobulin on Alzheimer's cerebrospinal fluid proteome.

Intravenous immunoglobulin (IVIg) therapy has shown promise in the treatment of Alzheimer's disease (AD). In this study, serial cerebrospinal fluid (CSF) samples from a group of subjects with AD undergoing IVIg immunotherapy are analyzed to identify IVIg-related changes. CSF samples from eight subjects were collected before therapy, after 6 months of therapy, and after a 3-month drug washout period. Samples were analyzed using a gel-based proteomics strategy and IVIg-related changes were determined by gel spot percent volumes. An initial assessment of the data revealed consistent and considerable change in 69 spots. A statistical analysis revealed 79 protein spots with a significant change after 6 months; furthermore, in a subset of these (25), the percent volume change was either maintained or reversed in the washout samples. The proteins that showed a significant change during IVIg therapy, including Ig molecules, gelsolin, transferrin, and transthyretin, have been previously implicated in AD. This study provides preliminary findings regarding a group of CSF proteins that may be associated with the treatment of AD, as well as the potential use of IVIg as an AD immunotherapy.

Longitudinal analysis of novel Alzheimer's disease proteomic cerebrospinal fluid biomarkers during intravenous immunoglobulin therapy.

Intravenous immunoglobulin (IVIg) therapy has shown promising results in treating Alzheimer's disease (AD). In this study, a Random Forest (RF) classification model was used to identify possible effects of IVIg on a group of eight subjects who underwent immunotherapy. Cerebrospinal fluid (CSF) samples from eight AD subjects who underwent IVIg therapy were collected before therapy, after 6 months of therapy, and after a 3-month drug washout period. Samples were analyzed using 2DE and further studied using a RF classification model to identify effects of IVIg on a panel of 23 putative diagnostic AD biomarkers previously identified. Six of the eight subjects showed improvements with respect to the 23 AD diagnostic biomarkers after 6 months of therapy compared to the samples taken at the outset of the trial. All subjects reverted back to baseline during drug washout. These results are also consistent with clinical observations. The observed improvements in subjects during 6 months of IVIg therapy and the reversion back to baseline during drug washout provides preliminary evidence regarding the potential use of IVIg as an AD immunotherapy.

18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease.

Intravenous immunoglobulin (IVIg) has been proposed as a potential agent for Alzheimer's disease (AD) immunotherapy because it contains antibodies against beta-amyloid (Abeta). We carried out an open label dose-ranging study in 8 mild AD patients in which IVIg was added to approved AD therapies for 6 months, discontinued, and then resumed for another 9 months. Infusions were generally well-tolerated. Anti-Abeta antibodies in the serum from AD patients increased in proportion to IVIg dose and had a shorter half-life than anti-hepatitis antibodies and total IgG. Plasma Abeta levels increased transiently after each infusion. Cerebrospinal fluid Abeta decreased significantly at 6 months, returned to baseline after washout and decreased again after IVIg was re-administered for an additional 9 months. Mini-mental state scores increased an average of 2.5 points after 6 months, returned to baseline during washout and remained stable during subsequent IVIg treatment. Our findings confirm and extend those obtained by Dodel et al. [Dodel, R.C., Du, Y., Depboylu, C., Hampel, H., Frolich, L., Haag, A., Hemmeter, U., Paulsen, S., Teipel, S.J., Brettschneider, S., Spottke, A., Nolker, C., Moller, H.J., Wei, X., Farlow, M., Sommer, N., Oertel, W.H., 2004. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 75, 1472-1474] from a 6-month trial of IVIg in 5 AD patients and justify further studies of IVIg for treatment of AD.