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

Relkin, Norman R.; Szabo, Paul; Adamiak, Basia; Burgut, Tuna; Monthe, Carmen; Lent, Richard W.; Younkin, Steven; Younkin, Linda; Schiff, Richard; Weksler, Marc E.

doi:10.1016/j.neurobiolaging.2007.12.021

« Previous Next »Neurobiology of Aging
Volume 30, Issue 11 , Pages 1728-1736, November 2009

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

Norman R. Relkin
- Department of Neurology, The Weill Cornell Medical College, New York, NY, USA
Paul Szabo
- Department of Neurology, The Weill Cornell Medical College, New York, NY, USA
- Department of Medicine, The Weill Cornell Medical College, New York, NY, USA
Basia Adamiak
- Department of Neurology, The Weill Cornell Medical College, New York, NY, USA
Tuna Burgut
- Department of Neurology, The Weill Cornell Medical College, New York, NY, USA
Carmen Monthe
- Department of Neurology, The Weill Cornell Medical College, New York, NY, USA
Richard W. Lent
- Department of Pathology and Laboratory Medicine, The Weill Cornell Medical College, New York, NY, USA
Steven Younkin
- The Mayo Clinic, Jacksonville, FL, USA
Linda Younkin
- The Mayo Clinic, Jacksonville, FL, USA
Richard Schiff
- Baxter BioScience, Westlake Village, CA, USA
Marc E. Weksler
- Department of Medicine, The Weill Cornell Medical College, New York, NY, USA
- Corresponding author at: Weill Medical College, 1300 York Avenue, New York, NY, USA. Tel.: +1 212 794 6478; fax: +1 212 746 6382.

Received 5 August 2007; received in revised form 4 December 2007; accepted 21 December 2007. published online 22 February 2008.

Abstract

Intravenous immunoglobulin (IVIg) has been proposed as a potential agent for Alzheimer's disease (AD) immunotherapy because it contains antibodies against beta-amyloid (Aβ). 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-Aβ 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 Aβ levels increased transiently after each infusion. Cerebrospinal fluid Aβ 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.

Keywords: Intravenous immunoglobulin, Alzheimer's disease, Amyloid beta peptides, Immunotherapy