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. The purpose of this study was to examine serum antibody levels to bacteria of periodontal disease in participants who eventually converted to Alzheimer’s disease (AD) compared to the antibody levels in control subjects. Methods Serum from 158 participants in the BRAINS (Biologically Resilient Adults in Neurological Studies) research program at the University of Kentucky were analyzed for IgG antibody levels to 7 oral bacteria associated with periodontitis including: Aggregati-bacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Tre-ponema denticola, Fusobacterium nucleatum, Tannerella forsythia, and Prevotella intermedia. All 158 participants were cognitively intact at baseline venous blood draw. Eighty one of the participants developed either mild-cognitive impairment (MCI) or Alz-heimer’s disease (AD) or both, and 77 controls remained cognitively intact in the years of follow up. Antibody levels were compared between controls and AD subjects at baseline draw and after conversion and controls and MCI subjects 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 AD patients compared to controls. These results remained significant when controlling for baseline age, Mini-Mental State Exam (MMSE) score and apolipoprotein epsilon 4 (APOE ε4) status. Conclusions This study provides initial data that demonstrate elevated antibodies to periodontal disease bacteria in subjects years prior 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.

Inflammasome Involvement in Alzheimer’s Disease

“…This study supports the literature on elevated antibodies to periodontal diseaseassociated bacteria such as P. gingivalis, being found in AD patients (7). Furthermore, in 2,355 people 60 years and over, the third NHANES study found associations between periodontitis and cognitive impairment and between measures of immunoglobulin to P. gingivalis and cognitive test performance (96,97). In this study all participants were cognitively intact at baseline.…”

“…In the NHANES study antibody levels to these organisms were significantly increased (α = 0.05) at baseline serum in patients with AD compared to controls (97). The results were significant after controlling for baseline age, Mini-Mental State Examination score, and allele APOEɛ4 status.…”

Multiple Sclerosis and Dentistry: A Contemporary Evaluation

“…When compared to the healthy individuals, people with AD had elevated plasma Ig G and TNF-α levels against periodontal bacteria (P. gingivalis, T. forsythia ve A. actinomycetemcomitans), There were no differences found in IL-1β and IL-6 levels (46). In a similar study, levels of F. nucleatum and P. intermedia antibodies seen in periodontal diseases were found to be elevated in people with AD compared to controls (47). The fact that periodontal diseases can be treated or managed suggested that they may pose a changeable risk factor for AD (48).…”

“…It was shown that periodontal treatment may lead to favorable systemic CRP levels (43,45). The possible relationships with Alzheimer's disease (AD), which is a neurodegenerative disease, and periodontal diseases, have also been investigated (46,47,48). When compared to the healthy individuals, people with AD had elevated plasma Ig G and TNF-α levels against periodontal bacteria (P. gingivalis, T. forsythia ve A. actinomycetemcomitans), There were no differences found in IL-1β and IL-6 levels (46).…”

Oral Surgery in the Human Microbiota Era the role of Periodontal Bacteria

“…(iii) the latest works report them as etiological agents in systemic infective-inflammatory or in autoimmune diseases such as rheumatoid arthritis and in atheromatous plaques [5][6][7], infective endocarditis and some researchers have recently suggested their role in neurogenerative diseases such as Alzheimer's disease [8], while it is certain that F. nucleatum is associated with intestinal cancer.…”