title: 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.
authors: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois 60612, USA. nlurain@rush.edu
authors: Nell S
authors: NS
authors: Lurain
authors: Barbara A
authors: BA
authors: Hanson
authors: Jeffrey
authors: J
authors: Martinson
authors: Sue E
authors: SE
authors: Leurgans
authors: Alan L
authors: AL
authors: Landay
authors: David A
authors: DA
authors: Bennett
authors: Julie A
authors: JA
authors: Schneider
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis; D000914:Antibodies, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology*; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000134:cerebrospinal fluid; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D000914:Antibodies, Viral; D007371:Interferon-gamma
keywords: Alzheimer's disease; CD28-/CD57+ T cells; amyloid-β; cytomegalovirus; interferon-gamma
references: Neurosci Lett. 2007 Dec 18;429(2-3):95-100
references: 17980964
references: Immunology. 2011 Mar;132(3):326-39
references: 21214539
references: Immun Ageing. 2011 Oct 28;8(1):10
references: 22035114
references: J Psychiatr Res. 2007 Oct;41(8):694-701
references: 16542679
references: J Alzheimers Dis. 2009;16(2):341-50
references: 19221424
references: J Virol. 2007 Jul;81(14):7759-65
references: 17409149
references: J Immunol. 2006 Feb 15;176(4):2645-53
references: 16456027
references: J Leukoc Biol. 2010 Jan;87(1):107-16
references: 19880576
references: Neurobiol Aging. 2000 May-Jun;21(3):383-421
references: 10858586
references: Curr Opin Immunol. 2009 Aug;21(4):440-5
references: 19535233
references: FASEB J. 1999 Jan;13(1):63-8
references: 9872930
references: Eur J Neurol. 2009 Jan;16(1):48-53
references: 19087150
references: Herpesviridae. 2011 Apr 07;2(1):6
references: 21473750
references: Curr Opin Immunol. 2010 Aug;22(4):529-34
references: 20685099
references: J Neurosci Res. 2012 May;90(5):1020-9
references: 22252837
references: J Am Geriatr Soc. 2006 Jul;54(7):1046-54
references: 16866674
references: Aging Cell. 2004 Aug;3(4):169-76
references: 15268750
references: J Virol. 2013 Jan;87(2):779-89
references: 23115277
references: J Virol. 2012 Jan;86(2):854-64
references: 22090104
references: J Immunol. 2010 Oct 15;185(8):4618-24
references: 20855876
references: J Immunol. 2010 Mar 15;184(6):3242-9
references: 20173031
references: Microbiol Mol Biol Rev. 2001 Jun;65(2):208-31 ; first and second pages, table of contents
references: 11381100
references: J Pathol. 2002 Jul;197(3):395-402
references: 12115887
references: Clin Infect Dis. 2006 Nov 1;43(9):1143-51
references: 17029132
references: J Infect Dis. 2010 Sep 1;202(5):690-9
references: 20632887
references: Transplant Proc. 2011 May;43(4):1233-5
references: 21620098
references: J Neurosci. 2003 Oct 29;23(30):9796-804
references: 14586007
references: Curr Opin Immunol. 2005 Oct;17(5):480-5
references: 16098721
references: J Clin Virol. 2006 Feb;35(2):226-31
references: 16386462
references: Clin Vaccine Immunol. 2012 May;19(5):772-9
references: 22398244
references: Ther Adv Neurol Disord. 2010 May;3(3):141-52
references: 21179606
references: J Infect Dis. 2011 May 15;203(10):1474-83
references: 21502083
references: J Immunol. 2004 Dec 15;173(12):7481-9
references: 15585874
references: J Gen Virol. 2011 Dec;92(Pt 12):2746-2756
references: 21813708
references: Neuroepidemiology. 2006;27(3):169-76
references: 17035694
references: Neurobiol Aging. 2012 Feb;33(2):430.e19-33
references: 21272962
references: PLoS One. 2011;6(10):e25152
references: 22003387
references: Psychol Aging. 2002 Jun;17(2):179-93
references: 12061405
references: Bone Marrow Transplant. 2010 Jun;45(6):979-84
references: 20190836
references: J Med Virol. 1993 Sep;41(1):24-9
references: 8228933
references: PLoS One. 2008;3(11):e3637
references: 18982063
references: Arch Neurol. 2004 Mar;61(3):378-84
references: 15023815
references: Immunol Cell Biol. 2005 Apr;83(2):182-8
references: 15748215
references: J Virol. 2005 Mar;79(6):3675-83
references: 15731261
references: Am J Epidemiol. 2010 May 15;171(10):1144-52
references: 20400465
references: Pediatr Int. 2009 Aug;51(4):530-4
references: 19438828
references: J Immunol. 1995 Nov 15;155(10):5046-56
references: 7594513