Intravenous immunoglobulin (IVIG) products are prepared from purified plasma 
immunoglobulins from large numbers of healthy donors. Pilot studies with the 
IVIG preparations Octagam and Gammagard in individuals with mild-to-moderate 
Alzheimer's disease (AD) suggested stabilization of cognitive functioning in 
these patients, and a phase II trial with Gammagard reported similar findings. 
However, subsequent reports from Octagam's phase II trial and Gammagard's phase 
III trial found no evidence for slowing of AD progression. Although these recent 
disappointing results have reduced enthusiasm for IVIG as a possible treatment 
for AD, it is premature to draw final conclusions; a phase III AD trial with the 
IVIG product Flebogamma is still in progress. IVIG was the first attempt to use 
multiple antibodies to treat AD. This approach should be preferable to 
administration of single monoclonal antibodies in view of the multiple processes 
that are thought to contribute to AD neuropathology. Development of 
"AD-specific" preparations with higher concentrations of selected human 
antibodies and perhaps modified in other ways (such as increasing their 
anti-inflammatory effects and/or ability to cross the blood-brain barrier) 
should be considered. Such preparations, if generated with recombinant 
technology, could overcome the problems of high cost and limited supplies, which 
have been major concerns relating to the possible widespread use of IVIG in AD 
patients. This review summarizes the recent AD IVIG trials and discusses the 
major issues relating to possible use of IVIG for treating AD, as well as the 
critical questions which remain.