title: Increase in the IgG avidity index due to herpes simplex virus type 1 reactivation and its relationship with cognitive function in amnestic mild cognitive impairment and Alzheimer's disease.
abstract: After infection with herpes simplex virus type 1 (HSV-1), latent infection persists for life in the trigeminal ganglion and reactivation results in an outbreak of cold sores around the mouth. Many previous studies have reported HSV-1 reactivation to be a risk factor for Alzheimer's disease (AD). This study enrolled subjects with AD (n=85), subjects with amnestic mild cognitive impairment (aMCI; a prodromal stage of AD) (n=34), and healthy controls (n=28). The avidity index of anti-HSV-1 IgG antibodies--a known indicator of HSV-1 reactivation--was measured in order to clarify the relationship between HSV-1 reactivation and symptoms of cognitive function in AD. Cognitive function in AD and aMCI were evaluated using scores from the mini-mental state examination (MMSE) and frontal assessment battery (FAB). The results showed that the subjects with aMCI, for which cerebral function is better preserved than subjects with AD, had a higher anti-HSV-1 IgG antibody avidity index than the AD subjects or healthy controls. Furthermore, the anti-HSV-1 IgG antibody avidity index was even higher in the subjects with high MMSE scores on orientation to time and three-step command subscores. We observed a negative correlation between the anti-HSV-1 IgG antibody avidity index and plasma BDNF concentration, which is an indicator of encephalitis. This suggests that HSV-1 reactivation, as observed through an increase in the anti-HSV-1 IgG avidity index, does not progress to encephalitis. These results suggest that HSV-1 reactivation occurs from the stage of aMCI, which is prodromal to AD, and can affect AD symptoms without an intermediary stage of severe encephalitis. The study demonstrates that the anti-HSV-1 IgG antibody avidity index could be a useful biomarker for the early diagnosis of aMCI as well as AD, and suggests that antiviral medication to treat HSV-1 could play a role in preventing the onset of AD.
authors.affiliation: Department of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan. kobayashi-n@jikei.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nagata
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Shinagawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Oka
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tatebayashi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kondo
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D000647:Amnesia / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000915:Antibody Affinity; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D042241:Early Diagnosis; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014775:Virus Activation
chemical_list: D000914:Antibodies, Viral; D019208:Brain-Derived Neurotrophic Factor; D007074:Immunoglobulin G