Immunomodulation of memory-impairing protein tau in Alzheimer's disease

Neurodegeneration induced by misfolded tau protein and neuroinflammation represent the major hallmarks of human tauopathies including Alzheimer's disease (AD). While tau driven neurodegeneration significantly correlates with disease progression, inflammation is considered to be an important factor regulating the resistance or susceptibility to AD. The emerging evidence suggests that the genes related to immunity can influence neurodegeneration.

In order to determine the role of MHC class II in the tau neurofibrillary cascade, we generated and used transgenic lines expressing human truncated tau protein in either spontaneously hypertensive rat (SHR) or Wistar-Kyoto rat (WKY) genetic background.

Brains of WKY and SHR transgenic rats and their age-matched nontransgenic littermates were examined by immunohistochemistry and RT-PCR.

Our results clearly showed that genetic background determined the inflammatory pattern (MHC class II) induced by tau neurodegenerative cascade in the transgenic rats expressing human misfolded truncated tau.

Using two transgenic rat lines with different immunogenetic backgrounds, expressing the same transgene, we conclude that genetic background is a potent modifier of the type of the immune response induced by tau neurodegeneration.