title: Reactivation of HSV-1 in the brain of patients with familial Alzheimer's disease.
abstract: Herpes simplex virus type 1 (HSV-1) has been proposed as an environmental risk factor for sporadic Alzheimer's disease, although this issue is still in dispute. The involvement of HSV-1 in the pathogenesis of familial Alzheimer's disease, the uncommon type of Alzheimer's disease, has not been addressed yet. We investigated formalin-fixed, paraffin-embedded, postmortem brain tissue sections of three patients with familial Alzheimer's disease for the presence of HSV-1 DNA. The nested polymerase chain reaction (PCR) detected the HSV-1 glycoprotein D gene in the brain of all three patients with familial Alzheimer's disease preferentially in the frontal and temporal cortices, whereas only one case out of six age-matched, non-Alzheimer's disease individuals could disclose the presence of HSV-1 gene. The PCR detected HSV-1 DNA in the frontal cortex of the two patients with sporadic Alzheimer's disease. The presence of HSV-1 was associated with beta-amyloid deposition in the cerebral cortex. To clarify the localization of HSV-1 in the brain tissue of patients with familial Alzheimer's disease, the in situ hybridization of the tyramide signal amplification system was used. It detected the HSV-1-specific signals predominantly in the cytoplasm of cortical neurons in a dot-like staining fashion. In addition, high-sensitivity immunohistochemistry revealed the existence of HSV-1 antigens in the cytoplasm of cortical neurons. This report provides the first evidence of reactivation of HSV-1 in the brain of patients with familial Alzheimer's disease, associated with beta-amyloid deposition, and suggests the possible involvement of HSV-1 together with genetic factors in the pathogenesis of familial Alzheimer's disease.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Mori
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kimura
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Rokuro
authors.initials: R
authors.lastname: Matsubara
authors.forename: Tohru
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nishiyama
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000821:virology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D019921:Biotinylation; D001921:Brain / Q000378:metabolism / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016133:Polymerase Chain Reaction / Q000379:methods; D014439:Tyramine / Q000031:analogs & derivatives; D014759:Viral Envelope Proteins / Q000235:genetics; D014775:Virus Activation
chemical_list: D016229:Amyloid beta-Peptides; D004279:DNA, Viral; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D014439:Tyramine