Virological and Immunological Characteristics of Human Cytomegalovirus Infection Associated With Alzheimer Disease

• Published in: The Journal of infectious diseases Vol. 208; no. 4; pp. 564 - 572
• Main Authors: Lurain, Nell S., Hanson, Barbara A., Martinson, Jeffrey, Leurgans, Sue E., Landay, Alan L., Bennett, David A., Schneider, Julie A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.08.2013
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - complications; Alzheimer Disease - pathology; Alzheimers disease; Amyloid beta-Peptides - analysis; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - cerebrospinal fluid; Biological and medical sciences; Cerebrospinal fluid; Cytomegalovirus; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - virology; Female; Fibroblasts - chemistry; Fibroblasts - virology; Fundamental and applied biological sciences. Psychology; Herpes simplex virus 1; Human cytomegalovirus; Human herpesvirus 1; Humans; Infections; Infectious diseases; Interferon-gamma - cerebrospinal fluid; Major and Brief Reports; Male; Medical sciences; Microbiology; Miscellaneous; Neurofibrillary Tangles - metabolism; Pathology; Phenotypes; T lymphocytes; T-Lymphocyte Subsets - immunology; Viral diseases; Virology; VIRUSES; Virus; Infection; Nervous system diseases; Alzheimer disease; Herpesviridae; Viral disease; Central nervous system disease; Degenerative disease; Betaherpesvirinae; Cerebral disorder; Human cytomegalovirus; amyloid-β; CD28-/CD57+ T cells; cytomegalovirus; Alzheimer's disease; interferon-gamma
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jit210

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.