Alzheimer's disease (AD) is a chronic
neurodegenerative disease associated with intracerebral accumulation of aggregated
amyloid-beta (Aβ) and
tau proteins, as well as
neuroinflammation.
Human intravenous immunoglobulin (
IVIG) is a mixture of polyclonal
IgG antibodies isolated and pooled from thousands of healthy human donors. The scientific rationale for testing
IVIG as a potential AD treatment include its natural anti-Aβ antibody activity, its favorable safety profile and inherent anti-inflammatory/immunomodulatory properties. Over the past decade, several clinical and pre-clinical experimental findings, advanced our knowledge about biological and therapeutic properties of
IVIG that are relevant to AD
therapy. Anti-
amyloid antibodies in
IVIG show significantly higher binding avidity for
amyloid oligomers and fibrils than for Aβ monomers. In a double transgenic murine model of AD, intracerebral injection of
IVIG causes suppression of Aβ fibril pathology whereas long term peripheral
IVIG treatments causes elevation of total brain Aβ levels with no measurable impact on Aβ deposits or tendency for inducing cerebral microhemmorhage. Furthermore, chronic
IVIG treatment suppressed
neuroinflammation and fostered adult hippocampal neurogenesis. In clinical studies with AD patients,
IVIG showed an acceptable safety profile and has not been reported to increase the incidence of
amyloid related imaging abnormalities. Preliminary studies on small number of patients reported clinical benefits in mild to moderate stage AD patients. However, double blind, placebo controlled studies later did not replicate those initial findings. Interestingly though, in
APOE4 carriers and in moderate disease stage subgroups, positive cognitive signals were reported. Nevertheless, both clinical and experimental (mouse) studies show that
antibodies in
IVIG can accumulate in CNS and its biological activities include neutralization of Aβ oligomers, suppression of
neuroinflammation and
immunomodulation. Identifying mediators of
IVIG's effects at the cellular and molecular level is warranted. In light of its favourable safety profile and aforementioned biological properties,
IVIG is still an enigmatic experimental candidate with enormous potential for being an AD therapeutic.