Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages

Ran Nie, Zhou Wu, Junjun Ni, Fan Zeng, Weixian Yu, Yufeng Zhang, Tomoko Kadowaki, Haruhiko Kashiwazaki, Jessica L. Teeling, Yanmin Zhou

Research output: Contribution to journalArticle

Abstract

Abnormal accumulation of amyloid-β (Aβ) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aβ in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aβ is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aβ metabolism is unknown. We hypothesized that chronic P. gingivalis infection expands Aβ pools in peripheral inflammatory tissues and thereby contributes to the accumulation of Aβ in the brain of patients with periodontitis. We showed that the increased expression of IL-1β, AβPP770, CatB, Aβ1-42, and Aβ3-42 was mainly co-localized with macrophages in the liver of P. gingivalis infected mice. Blocking CatB and NF-κB significantly inhibited the P. gingivalis-induced expression of IL-1β, AβPP770, Aβ1-42, and Aβ3-42 in RAW264.7 cells. Aβ3-42, but not Aβ1-42, induced the significant death of macrophages, and the reduction of phagocytic abilities induced by Aβ3-42 tended to be higher than that induced by Aβ1-42. Additionally, the expression of AβPP770, CatB, Aβ1-42, and Aβ3-42 was determined in the macrophages of gingival tissues from periodontitis patients. These findings indicate that chronic systemic P. gingivalis infection induces the Aβ accumulation in inflammatory monocytes/macrophages via the activation of CatB/NF-κB signaling, thus suggesting monocytes/macrophages serve as a circulating pool of Aβ in patients with periodontitis. Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression.

Original languageEnglish
Pages (from-to)479-494
Number of pages16
JournalJournal of Alzheimer's disease : JAD
Volume72
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Porphyromonas gingivalis
Amyloid
Monocytes
Periodontitis
Macrophages
Infection
Brain
Interleukin-1
Alzheimer Disease
Aptitude
Macrophage Activation
Lipopolysaccharides
Liver
Research

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages. / Nie, Ran; Wu, Zhou; Ni, Junjun; Zeng, Fan; Yu, Weixian; Zhang, Yufeng; Kadowaki, Tomoko; Kashiwazaki, Haruhiko; Teeling, Jessica L.; Zhou, Yanmin.

In: Journal of Alzheimer's disease : JAD, Vol. 72, No. 2, 01.01.2019, p. 479-494.

Research output: Contribution to journalArticle

Nie, R, Wu, Z, Ni, J, Zeng, F, Yu, W, Zhang, Y, Kadowaki, T, Kashiwazaki, H, Teeling, JL & Zhou, Y 2019, 'Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages', Journal of Alzheimer's disease : JAD, vol. 72, no. 2, pp. 479-494. https://doi.org/10.3233/JAD-190298
Nie, Ran ; Wu, Zhou ; Ni, Junjun ; Zeng, Fan ; Yu, Weixian ; Zhang, Yufeng ; Kadowaki, Tomoko ; Kashiwazaki, Haruhiko ; Teeling, Jessica L. ; Zhou, Yanmin. / Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages. In: Journal of Alzheimer's disease : JAD. 2019 ; Vol. 72, No. 2. pp. 479-494.
@article{410175490cc64f6da6430ab060deb97c,
title = "Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages",
abstract = "Abnormal accumulation of amyloid-β (Aβ) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aβ in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aβ is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aβ metabolism is unknown. We hypothesized that chronic P. gingivalis infection expands Aβ pools in peripheral inflammatory tissues and thereby contributes to the accumulation of Aβ in the brain of patients with periodontitis. We showed that the increased expression of IL-1β, AβPP770, CatB, Aβ1-42, and Aβ3-42 was mainly co-localized with macrophages in the liver of P. gingivalis infected mice. Blocking CatB and NF-κB significantly inhibited the P. gingivalis-induced expression of IL-1β, AβPP770, Aβ1-42, and Aβ3-42 in RAW264.7 cells. Aβ3-42, but not Aβ1-42, induced the significant death of macrophages, and the reduction of phagocytic abilities induced by Aβ3-42 tended to be higher than that induced by Aβ1-42. Additionally, the expression of AβPP770, CatB, Aβ1-42, and Aβ3-42 was determined in the macrophages of gingival tissues from periodontitis patients. These findings indicate that chronic systemic P. gingivalis infection induces the Aβ accumulation in inflammatory monocytes/macrophages via the activation of CatB/NF-κB signaling, thus suggesting monocytes/macrophages serve as a circulating pool of Aβ in patients with periodontitis. Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression.",
author = "Ran Nie and Zhou Wu and Junjun Ni and Fan Zeng and Weixian Yu and Yufeng Zhang and Tomoko Kadowaki and Haruhiko Kashiwazaki and Teeling, {Jessica L.} and Yanmin Zhou",
year = "2019",
month = "1",
day = "1",
doi = "10.3233/JAD-190298",
language = "English",
volume = "72",
pages = "479--494",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "2",

}

TY - JOUR

T1 - Porphyromonas gingivalis Infection Induces Amyloid-β Accumulation in Monocytes/Macrophages

AU - Nie, Ran

AU - Wu, Zhou

AU - Ni, Junjun

AU - Zeng, Fan

AU - Yu, Weixian

AU - Zhang, Yufeng

AU - Kadowaki, Tomoko

AU - Kashiwazaki, Haruhiko

AU - Teeling, Jessica L.

AU - Zhou, Yanmin

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Abnormal accumulation of amyloid-β (Aβ) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aβ in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aβ is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aβ metabolism is unknown. We hypothesized that chronic P. gingivalis infection expands Aβ pools in peripheral inflammatory tissues and thereby contributes to the accumulation of Aβ in the brain of patients with periodontitis. We showed that the increased expression of IL-1β, AβPP770, CatB, Aβ1-42, and Aβ3-42 was mainly co-localized with macrophages in the liver of P. gingivalis infected mice. Blocking CatB and NF-κB significantly inhibited the P. gingivalis-induced expression of IL-1β, AβPP770, Aβ1-42, and Aβ3-42 in RAW264.7 cells. Aβ3-42, but not Aβ1-42, induced the significant death of macrophages, and the reduction of phagocytic abilities induced by Aβ3-42 tended to be higher than that induced by Aβ1-42. Additionally, the expression of AβPP770, CatB, Aβ1-42, and Aβ3-42 was determined in the macrophages of gingival tissues from periodontitis patients. These findings indicate that chronic systemic P. gingivalis infection induces the Aβ accumulation in inflammatory monocytes/macrophages via the activation of CatB/NF-κB signaling, thus suggesting monocytes/macrophages serve as a circulating pool of Aβ in patients with periodontitis. Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression.

AB - Abnormal accumulation of amyloid-β (Aβ) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aβ in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aβ is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aβ metabolism is unknown. We hypothesized that chronic P. gingivalis infection expands Aβ pools in peripheral inflammatory tissues and thereby contributes to the accumulation of Aβ in the brain of patients with periodontitis. We showed that the increased expression of IL-1β, AβPP770, CatB, Aβ1-42, and Aβ3-42 was mainly co-localized with macrophages in the liver of P. gingivalis infected mice. Blocking CatB and NF-κB significantly inhibited the P. gingivalis-induced expression of IL-1β, AβPP770, Aβ1-42, and Aβ3-42 in RAW264.7 cells. Aβ3-42, but not Aβ1-42, induced the significant death of macrophages, and the reduction of phagocytic abilities induced by Aβ3-42 tended to be higher than that induced by Aβ1-42. Additionally, the expression of AβPP770, CatB, Aβ1-42, and Aβ3-42 was determined in the macrophages of gingival tissues from periodontitis patients. These findings indicate that chronic systemic P. gingivalis infection induces the Aβ accumulation in inflammatory monocytes/macrophages via the activation of CatB/NF-κB signaling, thus suggesting monocytes/macrophages serve as a circulating pool of Aβ in patients with periodontitis. Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression.

UR - http://www.scopus.com/inward/record.url?scp=85075813641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075813641&partnerID=8YFLogxK

U2 - 10.3233/JAD-190298

DO - 10.3233/JAD-190298

M3 - Article

C2 - 31594220

AN - SCOPUS:85075813641

VL - 72

SP - 479

EP - 494

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 2

ER -