Study Shows Not All IVIG Products Are Effective in Treating Alzheimer’s

A recent study has found that one specific intravenous immune globulin (IVIG) product was more effective than others in counteracting the cognitive deficits, ameliorating b-amyloid (Ab) deposits and tau phosphorylation among mice with Alzheimer disease (AD).

Because a growing body of research also shows that AD development is significantly impacted by inflammation, investigators have begun evaluating the use of IVIG in AD. In 2002, researchers showed IVIG contains anti-Ab antibodies and, since then, a variety of AD-relevant antibodies were found in IVIG, including anti-tau antibodies and anti-advanced glycation end-product receptor antibodies. Yet, clinical trials with IVIG for AD have shown inconsistent effects. At least five randomized controlled trials of IVIG for patients with AD have been conducted globally since 2013, but they have had varying results.

In this new study, investigators examined the neuroprotective effects of IVIG from three different manufacturers in triple-transgenic (3xTg-AD) mice. Behavioral tests, enzyme-linked immunosorbent assay, Luminex, immunohistochemistry, proteomics and parallel reaction monitoring were used to determine whether the three IVIG products had different efficacy on AD. Additionally, part of the potential mechanisms of action were revealed.

The three kinds of IVIG were numbered IVIG-A, IVIG-B and IVIG-C and were produced by different manufacturers in China. Their preparation processes are not identical and, notably, the plasma donors have great differences in race, ethnicity, geography and diet. Three mice from each IVIG group were examined and the whole brain was taken to detect human IgG (hIgG). Interestingly, the hIgG concentrations in IVIG-C and IVIG-A were significantly higher than the concentrations in IVIG-B. After intraperitoneal injection of IVIG into the mice, the bioavailability of the three IVIG products was different.

The three products also improved cognitive decline in 3xTg-AD mice to different degrees. After the IVIG injection and another three months of normal feeding, all mice were tested for cognitive behavior. When placed in a new environment, the 3xTg-AD mice traveled a less total distance compared with the control group, and the 3xTg-AD mice spent less time exploring a novel object used to evaluate recognition memory. Based on these findings, the investigators concluded that IVIG-C improved cognitive and motor decline in three behavioral outcomes, while IVIG-A and IVIG-B only improved the motor and autonomous decline in an open-field experiment test.

Based on these findings, the investigators concluded that IVIG-C was the only product to show overall improvement in neuroprotection, including alleviating cognitive decline, ameliorating Ab deposition and tau phosphorylation, attenuating microglia and astrocyte activation, and inhibiting the secretion and expression of pro-inflammatory factors. The results do importantly suggest that IVIG has promising therapeutic effects in AD treatment, although further research is necessary to understand the molecular mechanism of IVIG-C against AD.