Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

Solomon B.

Department of Molecular Microbiology and Biotechnology, George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.

Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

1989;3(2):95-101.

Increase of immunoglobulin G3 subclass is related to brain autoantibody in Alzheimer's disease but not in Down's syndrome.

Singh VK,

Medical University of South Carolina, Department of Microbiology and Immunology, Charleston 29425.

The proportions of IgG subclasses (G1, G2, G3 and G4) were quantified in sera from Alzheimer's disease (AD) patients, older Down's syndrome (DS) patients and age-matched controls. The levels of IgG1, IgG2 and IgG4 were normal in AD patients, but the proportions of IgG3 were significantly elevated in 9 of 20 (45%) patients (0.803 +/- 0.141 mg/ml; p less than 0.001) compared to the level found in age-matched controls (0.471 +/- 0.161 mg/ml; n = 10). The IgG3 level in the remaining 11 AD patients was slightly lower than the controls (0.385 +/- 0.104 vs. 0.471 +/- 0.161 mg/ml), but it did not reach statistical significance (p = 0.149). In contrast, patients with DS displayed imbalance of IgG2, IgG3, and IgG4 subclasses; they had significantly increased IgG3 but decreased IgG2 and IgG4 levels. The IgG1 level was within normal range. Moreover, a majority of AD sera (8 of 9) with elevated IgG3 concentration were positive for brain autoantibody. The remaining 11 AD sera without elevated IgG3 level, all DS sera and all control sera were negative for brain autoantibody. This finding indirectly suggests that brain autoantibody is mainly due to IgG3 subclass, at least in one subset of AD patients.

: Relationship between autoimmune thyroid disease Rand Alzheimer's disease.

Genovesi G,

Chair of Endocrine Physiopathology, University of Rome La Sapienza, Italy.

Alzheimer's Disease (AD) is a particular form of degenerative dementia probably due to deposit in the brain cortex of a non soluble protein called beta-A4 amyloid in senile plaque form. beta A4 is an aberrant mutant proteolytic product of Amyloid Protein Precursor (APP) codified on chromosome 21. Trisomy 21 is responsible for Down's Syndrome (DS). Down's patients have been shown to develop a form of Alzheimer's after 50 years of age, and high blood levels of antithyroid antibodies are also present in a significant percentage of these cases. In the present investigation, antithyroid antibody titres have been studied by means of RIA in group of 34 AD patients. As compared to 30 non-demented controls, AD subjects showed a significant increase in the mean values of antithyroglobulin (TgAb) and antimicrosomial (MCSAb) autoantibodies.