Telomere shortening in T cells correlates with Alzheimer’s disease status

Panossian, L.A; Porter, V.R; Valenzuela, H.F; Zhu, X; Reback, Erin; Masterman, D; Cummings, J.L; Effros, R.B

« Previous Next »Neurobiology of Aging
Volume 24, Issue 1 , Pages 77-84, January 2003

Telomere shortening in T cells correlates with Alzheimer’s disease status

L.A Panossian
- Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
V.R Porter
- Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA
H.F Valenzuela
- Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
X Zhu
- Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
Erin Reback
- Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA
D Masterman
- Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA
J.L Cummings
- Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA
R.B Effros
- Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
- Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA
- Corresponding author. Tel.: +1-310-825-0748; fax: +1-310-267-2104.

Received 15 November 2001; received in revised form 3 January 2002; accepted 7 March 2002.

Abstract

Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, and therefore serve as markers of a cell’s replicative history. In vivo, clonal expansion of T cells during immune responses to both foreign and autoantigens is associated with telomere shortening. To investigate possible immune alterations in Alzheimer’s disease (AD) that might impact current vaccine-based therapeutic strategies, we analyzed telomere lengths in immune cell populations from AD patients. Our data show a significant telomere shortening in PBMC from AD versus controls (P=0.04). Importantly, telomere length of T cells, but not of B cells or monocytes, correlated with AD disease status, measured by Mini Mental Status Exam (MMSE) scores (P=0.025). T cell telomere length also inversely correlated with serum levels of the proinflammatory cytokine TNFα (a clinical marker of disease status), with the proportion of CD8+ T cells lacking expression of the CD28 costimulatory molecule, and with apoptosis. These findings suggest an immune involvement in AD pathogenesis.

Keywords: Alzheimer’s disease, Telomeres, T cells, Immune system