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

Neurobiol Aging. 2009 Nov;30(11):1728-36. doi: 10.1016/j.neurobiolaging.2007.12.021. Epub 2008 Feb 21.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / immunology
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Male
  • Neurologic Examination
  • Peptide Fragments / cerebrospinal fluid
  • Psychiatric Status Rating Scales
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)