title: T-cells in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common dementing illness and is pathologically characterized by deposition of the 40-42 amino acid peptide, amyloid-beta (Abeta), as senile plaques. It is well documented that brain inflammatory mechanisms mediated by reactive glia are activated in response to Abeta plaques. A number of reports further suggest that T-cells are activated in AD patients, and that these cells exist both in the periphery and as infiltrates in the brain. We explore the potential role of T-cells in the AD process, a controversial area, by reviewing reports that show disturbed activation profiles and/or altered numbers of various subsets of T-cells in the circulation as well as in the AD brain parenchyma and in cerebral amyloid angiopathy. We also discuss the recent Abeta immunotherapy approach vis-à-vis the activated, autoaggressive T-cell infiltrates that contributed to aseptic meningoencephalitis in a small percentage of patients, and present possible alternative approaches that may be both efficacious and safe. Finally, we explore the use of mouse models of AD as a system within which to definitively test the possible contribution of T-cells to AD pathogenesis.
authors.affiliation: Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Mike
authors.initials: M
authors.lastname: Mullan
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016657:Cerebral Amyloid Angiopathy / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy; D008213:Lymphocyte Activation; D017628:Microglia / Q000276:immunology; D058225:Plaque, Amyloid / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*