Periodontal disease associates with higher brain amyloid load in normal elderly

Abstract

Background The accumulation of amyloid β plaques (Aβ) is a central feature of Alzheimer’s disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory/infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Methods Thirty-eight cognitively normal, healthy, community residing elderly (mean age 61; 68% female) were examined in an Alzheimer’s Disease research center and a University-based Dental School. Linear regression models (adjusted for age, ApoE and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using 11C-PIB PET imaging. Results After adjusting for confounders, clinical attachment loss (≥ 3mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased 11C-PIB uptake in Aβ vulnerable brain regions (p=0.002). Conclusion We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with prior animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations.

Effects of Tooth Loss and the Apolipoprotein E ɛ4 Allele on Mild Memory Impairment in the Fujiwara-kyo Study of Japan: A Nested Case-Control Study

“…In addition, antibody levels to Fusobacterium nucleatum and Prevotella intermedia , which are oral flora organisms, are significantly increased in serum collected at baseline before AD onset in AD patients compared to controls [14]. Periodontal disease, which is defined by clinical attachment loss, is associated with brain Aβ load [34]. Leptomeningeal cells transfer peripheral inflammatory signals from macrophages activated by lipopolysaccharides from Porphyromonas gingivalis , which is a major etiological agent of periodontal disease, to microglial cells [35].…”

Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer’s Disease?

“…First, there are significant correlations between the rate of cognitive decline and measures of periodontal disease progression, such as pocket depth, alveolar bone loss and tooth loss [37]. Currently, the relevance of newly identified risk factor, cognitive deficit for periodontitis [8], is more difficult to measure and pinpoint.…”

“…With regard specifically to periodontal disease, one longitudinal study has suggested a link between higher Aβ load in the hippocampus of elderly humans with mild forms of periodontitis [37]. Singhrao et al [58] are suggesting the role of P. gingivalis in inflammation mediated injury with progressive deterioration of the hippocampal microvascular integrity in the very regions of the brain that demonstrate a high burden of neuropathological hallmarks of AD.…”

Apolipoprotein E Related Co-Morbidities and Alzheimer’s Disease

“…More recent reports relating infections to a causative role in the onset of dementia are supported by Kamer et al [129] suggesting that mild periodontitis is associated with higher brain amyloid load in normal elderly subjects in the hippocampus.…”