Can Antibodies Against Glial Derived Antigens be Early Biomarkers of Hippocampal Demyelination and Memory Loss in Alzheimer's Disease?

BACKGROUND

Alzheimer's disease (AD) is known to exhibit well characterized pathologies including the extracellular accumulation of amyloid plaques, intra-axonal presence of neurofibrillary tangles, and glial hypertrophy. Nevertheless, the nature of myelin pathology in AD has not been well studied. Recent studies on animal models of AD, however, revealed focal demyelination within amyloid-β plaques in hippocampus.

OBJECTIVES

In a view of this finding, we decided to assess humoral response against proteins of myelin sheath in AD, in the hope of identifying early biomarkers of memory loss and neuropathological process characteristic of AD.

METHODS

We assessed antibodies levels against proteins of the myelin sheath: myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), and proteolipoprotein (PLP) in sera of 26 AD patients and 26 healthy controls, using commercially available ELISA system (Mediagnost, Germany).

RESULTS

In the AD patient subgroup, significantly higher titers were observed for all types of assessed IgG autoantibodies compared to healthy control subjects (anti-MOG, anti-MAG, anti-MBP, anti-PLP). The titers of most of the investigated IgM antibodies were also higher in AD patients (p <  0.05), with the exception of anti-MAG IgM antibodies (p >  0.05).

CONCLUSION

The study provides the evidence for the significantly increased production of autoantibodies against proteins of myelin sheath in AD. These results can be of importance in the light of emerging data from animal models of AD, indicating early demyelination of hippocampal region. Further studies on larger population are necessary to confirm whether these autoantibodies could serve as early biomarkers of AD in humans.