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T-cells in alzheimer’s disease

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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.

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Authors and Affiliations

  1. Section of Immunobiology, Yale University School of Medicine, 300 Cedar Street, 06520, New Haven, CT

    Terrence Town & Richard A. Flavell

  2. Neuroimmunology Laboratory, Department of Psychiatry, University of South Florida, 3515 E. Fletcher Avenue, 33613, Tampa, FL

    Jun Tan

  3. Howard Hughes Medical Institute, 06520, New Haven, CT

    Richard A. Flavell

  4. Roskamp Institute, 2040 Whitfield Avenue, 34243, Sarasota, FL

    Mike Mullan

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  1. Terrence Town
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  2. Jun Tan
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  3. Richard A. Flavell
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  4. Mike Mullan
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Correspondence to Mike Mullan.

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Town, T., Tan, J., Flavell, R.A. et al. T-cells in alzheimer’s disease. Neuromol Med 7, 255–264 (2005). https://doi.org/10.1385/NMM:7:3:255

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  • DOI: https://doi.org/10.1385/NMM:7:3:255

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