Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease

Abstract

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

Keywords: Alzheimer's disease; CD28-/CD57+ T cells; amyloid-β; cytomegalovirus; interferon-gamma.

Figure 1.

Induction of amyloid-β (Aβ) in human foreskin fibroblasts infected with cytomegalovirus (CMV) or herpes simplex virus type 1 (HSV-1). Isotype control is mouse immunoglobulin G (IgG) 1. A, CMV strain BI-1. B, CMV strain BI-4. C, CMV strain BI-6. CMV-infected monolayers were stained with anti-CMV antibody to immediate early/early antigen 6 days after inoculation. D, HSV-1 F strain, 24 hours after inoculation. E, HSV-1 F strain, 48 hours after inoculation. HSV-1–infected monolayers were stained with anti-HSV-1 antibody to VP5 antigen.