Telomere shortening in T cells correlates with Alzheimer's disease status.
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 TNFalpha (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.
Panossian
L A
LA
Department of Pathology, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Porter
V R
VR
Valenzuela
H F
HF
Zhu
X
X
Reback
Erin
E
Masterman
D
D
Cummings
J L
JL
Effros
R B
RB
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics* / Q000276:immunology; D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006360:Heat-Shock Proteins; D018869:Heat-Shock Response; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011569:Psychiatric Status Rating Scales; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019098:Telomerase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
D018106:CD28 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D006360:Heat-Shock Proteins; D010835:Phytohemagglutinins; D019098:Telomerase