title: CD45 isoform alteration in CD4+ T cells as a potential diagnostic marker of Alzheimer's disease.
abstract: Aging represents the greatest risk for development of Alzheimer's disease (AD), and changes in peripheral immune cell phenotypes have been found to be associated with aging. Using flow cytometry, we measured the relative expression levels of CD45 isoforms, a marker of nai;ve versus memory CD4+ T cell status, on isolated CD4+ T lymphocytes from patients with a clinical diagnosis of probable Alzheimer's disease, normal elderly, cognitively abnormal elderly, and patients with clinically diagnosed other forms of dementia. Data show significantly lower levels of CD45RA, and an increase in the CD45RO/CD45RA ratio, on CD4+ T cells in patients diagnosed with probable Alzheimer's disease (n=46) and in cognitively abnormal individuals (n=37) compared to age-matched normal participants (n=90). Patients diagnosed with other forms of dementia (n=19) did not significantly differ from normal individuals. Both CD45RA and the CD45RO/CD45RA ratio had higher positive and negative predictive values and were more sensitive biomarkers of probable AD than the apolipoprotein E epsilon 4 allele, and had greater predictive ability for probable AD by regression analyses. Additionally, a testing strategy employing apolipoprotein E genotyping and CD45RA or the CD45RO/CD45RA ratio revealed increased sensitivity, positive and negative predictive values, and predictive ability over the apolipoprotein E epsilon 4 allele. These data show altered peripheral immunity in AD patients, and raise the possibility that a testing strategy using CD45 isoform alteration on CD4+ T cells and apolipoprotein E genotype may be clinically valuable for diagnosing probable AD.
authors.affiliation: Department of Psychiatry, Roskamp Institute, University of South Florida, 3515 E. Fletcher Ave., Tampa, FL 33613, USA. jtan@hsc.usf.edu
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Laila
authors.initials: L
authors.lastname: Abdullah
authors.forename: Yajaun
authors.initials: Y
authors.lastname: Wu
authors.forename: Andon
authors.initials: A
authors.lastname: Placzek
authors.forename: Brent
authors.initials: B
authors.lastname: Small
authors.forename: Jodi
authors.initials: J
authors.lastname: Kroeger
authors.forename: Fiona
authors.initials: F
authors.lastname: Crawford
authors.forename: Dan
authors.initials: D
authors.lastname: Richards
authors.forename: Michael
authors.initials: M
authors.lastname: Mullan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D003072:Cognition Disorders / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood*; D008297:Male; D020033:Protein Isoforms
chemical_list: D015415:Biomarkers; D020033:Protein Isoforms; D017493:Leukocyte Common Antigens