Vaccination induced changes in pro-inflammatory cytokine levels as an early putative biomarker for cognitive improvement in a transgenic mouse model for Alzheimer disease

摘要

The initial observation of a potential role for inflammation in Alzheimer disease (AD) was noted by Alois Alzheimer and was suggested by the presence of "activated" glia in specific areas of the brain.1 However, as with other aspects of AD pathology, the molecular evidence for inflammation in AD came in the 1980s when associated amyloid deposits noted in this disease were found to contain, in addition to amyloid beta (Abeta) peptides, other proteins, including complement, HLA antigens, anti-chy-motrypsin, and IL-1, all of which are normally secreted during inflammation and the associated acute phase response. The strongest evidence that inflammation causally contributes to AD resulted from studies in transgenic (Tg) mice carrying a mutant human amyloid precursor protein (APP) gene as well as preseni-lin-1 (PS-1), in which accumulation of Ap and cognitive decline were demonstrated to be correlated with the presence of inflammation and associated cytokines and other proteins.