title: Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease.
abstract: BACKGROUND
  Chronic inflammation in periodontal disease has been suggested as a potential risk factor in Alzheimer's disease (AD). The purpose of this study was to examine serum antibody levels to bacteria of periodontal disease in participants who eventually converted to AD compared with the antibody levels in control subjects.
  
  
  METHODS
  Serum samples from 158 participants in the Biologically Resilient Adults in Neurological Studies research program at the University of Kentucky were analyzed for immunoglobulin G antibody levels to seven oral bacteria associated with periodontitis, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Treponema denticola, Fusobacterium nucleatum, Tannerella forsythia, and Prevotella intermedia. All 158 participants were cognitively intact at baseline venous blood draw. In all, 81 of the participants developed either mild cognitive impairment (MCI) or AD or both, and 77 controls remained cognitively intact in the years of follow-up. Antibody levels were compared between controls and subjects with AD at baseline draw and after conversion and controls and subjects with MCI at baseline draw and after conversion using the Wilcoxon rank-sum test. AD and MCI participants were not directly compared. Linear regression models were used to adjust for potential confounding.
  
  
  RESULTS
  Antibody levels to F nucleatum and P intermedia were significantly increased (α = 0.05) at baseline serum draw in the patients with AD compared with controls. These results remained significant when controlling for baseline age, Mini-Mental State Examination score, and apolipoprotein epsilon 4 status.
  
  
  CONCLUSIONS
  This study provides initial data that demonstrate elevated antibodies to periodontal disease bacteria in subjects years before cognitive impairment and suggests that periodontal disease could potentially contribute to the risk of AD onset/progression. Additional cohort studies profiling oral clinical presentation with systemic response and AD and prospective studies to evaluate any cause-and-effect association are warranted.
authors.affiliation: Department of Oral Health Science, College of Dentistry, University of Kentucky, Lexington, USA. pam.stein@uky.edu
authors.forename: Pamela
authors.initials: P
authors.lastname: Sparks Stein
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Steffen
authors.forename: Charles
authors.initials: C
authors.lastname: Smith
authors.forename: Gregory
authors.initials: G
authors.lastname: Jicha
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ebersole
authors.forename: Erin
authors.initials: E
authors.lastname: Abner
authors.forename: Dolph
authors.initials: D
authors.lastname: Dawson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000382:microbiology*; D000907:Antibodies, Bacterial / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D016866:Bacteroidaceae Infections / Q000097:blood / Q000150:complications / Q000276:immunology; D060825:Cognitive Dysfunction / Q000097:blood / Q000382:microbiology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D016966:Porphyromonas gingivalis / Q000276:immunology*; D018713:Prevotella intermedia / Q000276:immunology*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000907:Antibodies, Bacterial; D001057:Apolipoproteins E; D007074:Immunoglobulin G