Intravenous immunoglobulins for Alzheimer's disease

Lakshman Puli, Heikki Tanila, Norman Relkin
Current Alzheimer Research 2014, 11 (7): 626-36
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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"