Serum, CSF and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between CMV infection and clinical and pathological markers of Alzheimer's Disease (AD). CMV antibody levels were associated with neurofibrillary tangles (NFT). CSF interferon-γ was only detected in seropositive subjects and was significantly associated with NFT. The percentage of senescent T cells (CD4+ or CD8+/CD28-/CD57+) was significantly higher for CMV-seropositive compared to CMV-seronegative subjects, and marginally associated with the pathologic diagnosis of AD (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFF) infected with each of 3 clinical CMV strains. In the same subjects there was no association of HSV-1 antibody levels with CMV antibody levels or clinical or pathological markers of AD. HSV-1 infection of HFF did not induce amyloid-β. These data support an association of CMV with the development of AD.
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