T-Cells in Alzheimer's Disease

Author： Town Terrence Tan Jun Flavell Richard A. Mullan Mike

ISSN： 1535-1084

Source： NeuroMolecular Medicine, Vol.7, Iss.3, 2005-08, pp. : 255-264

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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-β (Aβ), as senile plaques. It is well documented that brain inflammatory mechanisms mediated by reactive glia are activated in response to Aβ 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 Aβ 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.