Apoptosis of CD4+ T and Natural Killer Cells in Alzheimer's Disease

K. Schindowski; J. Peters; C. Gorriz; U. Schramm; T. Weinandi; S. Leutner; K. Maurer; L. Frölich; W. E. Müller; A. Eckert

doi:10.1055/s-2006-954591

Pharmacopsychiatry 2006; 39(6): 220-228
DOI: 10.1055/s-2006-954591

Original Paper

Apoptosis of CD4⁺ T and Natural Killer Cells in Alzheimer's Disease

K. Schindowski¹ ^, ² , J. Peters³ , C. Gorriz³ ^, ⁶ , U. Schramm³ , T. Weinandi³ , S. Leutner¹ , K. Maurer³ , L. Frölich³ ^, ⁵ , W. E. Müller¹ , A. Eckert¹ ^, ⁴

¹Institute of Pharmacology, Biocenter, Johann Wolfgang-Goethe-University, Frankfurt, Germany
²Present address: INSERM U815, Université Lille 2, Faculté de Médecine, Institut de Médecine Prédictive et Recherche Thérapeutique, Lille Cedex, France
³Department of Psychiatry and Psychotherapy I, Johann Wolfgang-Goethe-University, Frankfurt, Germany
⁴Present address: Psychiatric University Clinic Basel, Basel, Switzerland
⁵Central Institute for Mental Health, Monnhein, Germany
⁶Department of Psychiatry, University Mainz, Mainz, Germany

Abstract

Background: Immunotherapy appears to be a potent treatment against Alzheimer's disease (AD), but the mechanisms underlying neural-immune interaction are still not known. Methods: Here, we determined cell death and distribution of lymphocyte subsets of peripheral blood mononuclear cells (PBMC) in AD and aging, e.g. T (CD4⁺CD3⁺, CD8⁺CD3⁺), B (CD19⁺) and NK (CD16⁺+CD56⁺) cells. Results: Increased apoptosis was found in CD4⁺ T and NK cells in AD, while in aging all subsets were affected. The expression of anti-apoptotic Bcl2 correlated with observed cell death in T-helper and B cells irrespective of dementia. The levels of Bcl2 in T-cells were significantly increased in mild AD. Apoptosis and Bcl2 levels were also elevated in the APP_751SL × PS1_M146L transgenic mouse model. Conclusion: The mechanisms triggering apoptosis and activation of lymphocytes in AD appear therefore to be different than those in immunosenescence and possibly bear an important biomarker to monitor immunotherapy in AD.

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Correspondence

Katharina Schindowski

INSERM U815

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