Neuromolecular Med. 2005;7(3):255-64
T-cells in Alzheimer's disease.
Town T, Tan J, Flavell
RA, Mullan M.
Section of Immunobiology,
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-a-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.
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Keywords: amyloid, Alzheimer's disease, T-cells, glia, and plaques