High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer’s and Parkinson’s disease

David C Emery; Maria Davies; Tanya L Cerajewska; Jelena Taylor; Mae Hazell; Alex R Paterson; Shelley J Allen Allen-Birt; Nicola X West

doi:10.3389/fnagi.2022.1026260

High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer’s and Parkinson’s disease

David C Emery, Maria Davies, Tanya L Cerajewska, Jelena Taylor, Mae Hazell, Alex R Paterson, Shelley J Allen Allen-Birt, Nicola X West^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

12 Citations (Scopus)

88 Downloads (Pure)

Abstract

Introduction: Alzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative conditions characterised by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis.

Methods: Here, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterise bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases.

Results and discussion: This study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease aetiology

Original language	English
Article number	1026260
Number of pages	25
Journal	Frontiers in Aging Neuroscience
Volume	14
DOIs	https://doi.org/10.3389/fnagi.2022.1026260
Publication status	Published - 9 Dec 2022

Bibliographical note

Funding Information:
The authors would like to thank Charlie Parkinson PhD, FRSC Medical Affairs Director Gum Health and Family Oral Health, and GlaxoSmithKline (GSK), St Georges Avenue, Weybridge, Surrey, KT13 0DE, United Kingdom for their disinterested support. We would like to thank the South West Dementia Brain Bank (SWDBB), their donors and donor’s families for providing brain tissue for this study. We thank BRACE and the Sigmund Gestetner Trust for all their support. Deborah K. Shoemark (Department of Biochemistry, University of Bristol) and SA-B were chief investigators for the South West-Cornwall and Plymouth REC ref.: 13/SW/0272 IRAS ID: 5875 which provided blood samples for comparative assessment in this study. Mrs. Helen Foskett, Oral and Dental Science Bristol Dental Hospital took blood samples during the study.

Funding Information:
We are most grateful to GlaxoSmithKline, for their equitable donation to support our work on Alzheimer’s disease and bacteraemia. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This was the sole source of funding. Tissue for this study was provided with support from the BDR programme, jointly funded by Alzheimer’s Society, United Kingdom and Alzheimer’s Society. The SWDBB is further supported by Bristol Research into Alzheimer’s and Care of the Elderly (BRACE)’. The University of Bristol acted as Research Sponsor from 04.12.2013, until 30.7.2019 with an HRA approved extension to 31.12.2020.

Publisher Copyright:
Copyright © 2022 Emery, Davies, Cerajewska, Taylor, Hazell, Paterson, Allen-Birt and West.

Research Groups and Themes

Cerebrovascular and Dementia Research Group

Keywords

16S rRNA NGS
Alzheimer’s
Parkinson’s
brain
oral bacteria

Access to Document

10.3389/fnagi.2022.1026260Licence: CC BY

Full-text PDF (final published version)
This is the final published version of the article (version of record). It first appeared online via Frontiers Media at https://doi.org/10.3389/fnagi.2022.1026260 .Please refer to any applicable terms of use of the publisher.
Final published version, 8.43 MBLicence: CC BY

Handle.net

Persistent link

Investigation of the potential role of oral pathogens in Parkinson's Disease
Taylor, J. (Author), West, N. X. (Supervisor) & Allen-Birt, S. J. A. (Supervisor), 21 Mar 2023
Student thesis: Master's Thesis › Master of Science by Research (MScR)

File

Cite this

@article{3bc93d59640d44cea1939f1f4d5fb213,

title = "High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer{\textquoteright}s and Parkinson{\textquoteright}s disease",

abstract = "Introduction: Alzheimer{\textquoteright}s (AD) and Parkinson{\textquoteright}s disease (PD) are neurodegenerative conditions characterised by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis. Methods: Here, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterise bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases. Results and discussion: This study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease aetiology",

keywords = "16S rRNA NGS, Alzheimer{\textquoteright}s, Parkinson{\textquoteright}s, brain, oral bacteria",

author = "Emery, {David C} and Maria Davies and Cerajewska, {Tanya L} and Jelena Taylor and Mae Hazell and Paterson, {Alex R} and Allen-Birt, {Shelley J Allen} and West, {Nicola X}",

note = "Funding Information: The authors would like to thank Charlie Parkinson PhD, FRSC Medical Affairs Director Gum Health and Family Oral Health, and GlaxoSmithKline (GSK), St Georges Avenue, Weybridge, Surrey, KT13 0DE, United Kingdom for their disinterested support. We would like to thank the South West Dementia Brain Bank (SWDBB), their donors and donor{\textquoteright}s families for providing brain tissue for this study. We thank BRACE and the Sigmund Gestetner Trust for all their support. Deborah K. Shoemark (Department of Biochemistry, University of Bristol) and SA-B were chief investigators for the South West-Cornwall and Plymouth REC ref.: 13/SW/0272 IRAS ID: 5875 which provided blood samples for comparative assessment in this study. Mrs. Helen Foskett, Oral and Dental Science Bristol Dental Hospital took blood samples during the study. Funding Information: We are most grateful to GlaxoSmithKline, for their equitable donation to support our work on Alzheimer{\textquoteright}s disease and bacteraemia. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This was the sole source of funding. Tissue for this study was provided with support from the BDR programme, jointly funded by Alzheimer{\textquoteright}s Society, United Kingdom and Alzheimer{\textquoteright}s Society. The SWDBB is further supported by Bristol Research into Alzheimer{\textquoteright}s and Care of the Elderly (BRACE){\textquoteright}. The University of Bristol acted as Research Sponsor from 04.12.2013, until 30.7.2019 with an HRA approved extension to 31.12.2020. Publisher Copyright: Copyright {\textcopyright} 2022 Emery, Davies, Cerajewska, Taylor, Hazell, Paterson, Allen-Birt and West.",

year = "2022",

month = dec,

day = "9",

doi = "10.3389/fnagi.2022.1026260",

language = "English",

volume = "14",

journal = "Frontiers in Aging Neuroscience",

issn = "1663-4365",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer’s and Parkinson’s disease

AU - Emery, David C

AU - Davies, Maria

AU - Cerajewska, Tanya L

AU - Taylor, Jelena

AU - Hazell, Mae

AU - Paterson, Alex R

AU - Allen-Birt, Shelley J Allen

AU - West, Nicola X

N1 - Funding Information: The authors would like to thank Charlie Parkinson PhD, FRSC Medical Affairs Director Gum Health and Family Oral Health, and GlaxoSmithKline (GSK), St Georges Avenue, Weybridge, Surrey, KT13 0DE, United Kingdom for their disinterested support. We would like to thank the South West Dementia Brain Bank (SWDBB), their donors and donor’s families for providing brain tissue for this study. We thank BRACE and the Sigmund Gestetner Trust for all their support. Deborah K. Shoemark (Department of Biochemistry, University of Bristol) and SA-B were chief investigators for the South West-Cornwall and Plymouth REC ref.: 13/SW/0272 IRAS ID: 5875 which provided blood samples for comparative assessment in this study. Mrs. Helen Foskett, Oral and Dental Science Bristol Dental Hospital took blood samples during the study. Funding Information: We are most grateful to GlaxoSmithKline, for their equitable donation to support our work on Alzheimer’s disease and bacteraemia. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This was the sole source of funding. Tissue for this study was provided with support from the BDR programme, jointly funded by Alzheimer’s Society, United Kingdom and Alzheimer’s Society. The SWDBB is further supported by Bristol Research into Alzheimer’s and Care of the Elderly (BRACE)’. The University of Bristol acted as Research Sponsor from 04.12.2013, until 30.7.2019 with an HRA approved extension to 31.12.2020. Publisher Copyright: Copyright © 2022 Emery, Davies, Cerajewska, Taylor, Hazell, Paterson, Allen-Birt and West.

PY - 2022/12/9

Y1 - 2022/12/9

N2 - Introduction: Alzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative conditions characterised by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis. Methods: Here, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterise bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases. Results and discussion: This study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease aetiology

AB - Introduction: Alzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative conditions characterised by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis. Methods: Here, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterise bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases. Results and discussion: This study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease aetiology

KW - 16S rRNA NGS

KW - Alzheimer’s

KW - Parkinson’s

KW - brain

KW - oral bacteria

U2 - 10.3389/fnagi.2022.1026260

DO - 10.3389/fnagi.2022.1026260

M3 - Article (Academic Journal)

C2 - 36570533

SN - 1663-4365

VL - 14

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

M1 - 1026260

ER -

High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer’s and Parkinson’s disease

Abstract

Bibliographical note

Research Groups and Themes

Keywords

Access to Document

Handle.net

Fingerprint

Student theses

Investigation of the potential role of oral pathogens in Parkinson's Disease

Cite this