Immunopathogenesis Of Alzheimer's Disease

Abstract

Alzheimer Disease (AD) is a multifactorius, complex syndrome, which probably comprises different etiopathogenetic subunits, to which a variety of risk factors contribute. The main histopathological hallmarks of AD are plaques and neurofibrillary tangles. Plaques are extracelluler deposits, consisting primarily of the amiloid beta (A-beta). Tangles are flamentous intraneuronal inclusions composed of hyper or abnormally phosphorylated microtubule associated protein tau (PH-tau) which lead to the death of the neurons within which they are formed. Neuronal fragments, found in association with a subset of plaques and thread fike* axonal and dentritic fragments scattered throughout the extracellular space, alsa contain PH-tau. The appearance of senil plaques containing dystrophic neurites, tau protein and abundant condensed Abeta deposits lead to the ultimate loss of neurons and synapses the correlate with the intellectual decline of AD patients. At present there seems to be no doubt that neuroimmun mechanism contribute actively to the neurodestructive process located in the senil plaques in the AD brain. The senil plaques contain deposits of many immun reactionsoluble factors. Among them, cytokines, chemokines, complement proteins and receptors, acute phase reactants were exclusively localized in the AD plaques. Microglia cells which are in the rim of senil plaques, are a major component of inflammation in the brain. Mutations in the APP, PS1, PS2 genes are associated with alterations in Abeta. These mutations shows significently enhanced A-beta and fosforile tau positive neurites. Apolipoprotein E4 (Apo E4) is associated with a significant risk for AD, particularly the late onset type of the disease. Several changes in immune parameters were also found in peripheral blood of AD patients. Laboratory investigation of peripheral blood revealed abnormalitiis of both humaral and celluler immunity in AD patients. Therefore we focus on the data on immunological changes found directly in the brain tissue to explain pathomechanism of AD, where as the results of peripheral blood estimations that in some cases of AD the systemic immunological alterations could be noticed alsa in peripheral blood, which confirms the immunopathomechanism of the disease.