T cell response to amyloid-beta and to mitochondrial antigens in Alzheimer's disease

Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer's disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1-42 of amyloid-beta (Abeta) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Abeta fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.