title: Amyloid beta (A4) precursor protein expression in human periodontitis-affected gingival tissues.
abstract: OBJECTIVE
  Periodontitis involves periodontal tissue destruction and is associated with chronic inflammation and ageing. Periodontitis has recently been recognised as a risk factor for Alzheimer's disease (AD). We showed upregulation of molecules in the AD pathway including amyloid beta (A4) precursor protein (APP), a key gene in AD, interleukin-1 beta (IL-1β), and complement component 1 (q subcomponent, A chain) (C1QA) in periodontitis compared to healthy tissues. Here, we quantitatively analysed the expression levels of APP, IL-1β, and C1QA and determined the localisation of APP in gingival tissues.
  
  
  METHODS
  Fourteen chronic periodontitis patients and 14 healthy participants were enrolled. Six samples of total RNA from two distinct sites of healthy and periodontitis-affected gingival tissues from three randomly selected patients were used for microarray analyses, and significant biological pathways in periodontitis were identified. Differential gene expression of APP, IL-1β, and C1QA, which belong to the AD pathway, were analysed with quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR) using samples from these 14 chronic periodontitis patients and 14 healthy controls. APP localisation was analysed with immunohistochemistry.
  
  
  RESULTS
  APP, IL-1β, and C1QA mRNA levels were significantly upregulated in periodontitis-affected gingival tissues. APP was mainly localised in macrophages in gingival connective tissues underneath the epithelial layers.
  
  
  CONCLUSIONS
  An association between AD and periodontitis was detected with microarray and computer-aided data mining analyses. qRT-PCR identified differential gene expression in periodontitis-affected gingival tissue that may be related to AD pathogenesis. Elevated APP, IL-1β, and C1QA transcripts and APP-expressing macrophages in periodontitis-affected gingival tissues were observed, suggesting a relationship between periodontitis and AD pathogenesis.
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Japan. Electronic address: kubota@dent.niigata-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata 951-8520, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Abe
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Morozumi
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nakasone
authors.affiliation: Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata 951-8520, Japan; Division of Oral Pathology, Department of Oral Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saku
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshie
mesh_terms: D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016022:Case-Control Studies; D003172:Complement C1 / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005881:Gingiva / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D010518:Periodontitis / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003172:Complement C1; D053583:Interleukin-1beta
keywords: Amyloid beta precursor protein; DNA microarrays; Gene expression; Periodontitis, Alzheimer's disease