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.