The University of Southampton
University of Southampton Institutional Repository

Microglial motility in Alzheimer’s disease and after aβ42 immunotherapy: a human post-mortem study

Microglial motility in Alzheimer’s disease and after aβ42 immunotherapy: a human post-mortem study
Microglial motility in Alzheimer’s disease and after aβ42 immunotherapy: a human post-mortem study
Microglial function is highly dependent on cell motility, with baseline motility required for homeostatic surveillance activity and directed motility to migrate towards a source of injury. Experimental evidence suggests impaired microglial motility in Alzheimer’s disease (AD) and therefore we have investigated whether the expression of proteins associated with motility is altered in AD and affected by the Aβ immunotherapy using post-mortem brain tissue of 32 controls, 44 AD cases, and 16 AD cases from our unique group of patients immunised against Aβ42 (iAD). Sections of brain were immunolabelled and quantified for (i) the motility-related microglial proteins Iba1, cofilin 1 (CFL1), coronin-1a (CORO1A) and P2RY12, and (ii) pan-Aβ, Aβ42 and phosphorylated tau (ptau). The neuroinflammatory environment was characterised using Meso Scale Discovery multiplex assays. The expression of all four motility-related proteins was unmodified in AD compared with controls, whereas Iba1 and P2RY12, the homeostatic markers, were increased in the iAD group compared with AD. Iba1 and P2RY12 showed significant positive correlations with Aβ in controls but not in the AD or iAD groups. Pro- and anti-inflammatory proteins were increased in AD, whereas immunotherapy appears to result in a slightly less pro-inflammatory environment. Our findings suggest that as Aβ appears during the ageing process, the homeostatic Iba1 and P2RY12 –positive microglia respond to Aβ, but this response is absent in AD. Aβ immunisation promoted increased Iba1 and P2RY12 expression, likely reflecting increased baseline microglial motility but without restoring the profile observed in controls
human microglia, cell motility, Alzheimer’s disease, Aβ immunotherapy, neuroinflammation
2051-5960
Franco Bocanegra, Diana, Karina
ad8042ca-0800-495e-a32c-1bdca88aacaa
George, Bethany
41348dd8-14c2-4ec6-a766-9086e1f597d5
Lau, Laurie C.
2af8045d-6162-4939-aba7-28dd2f60f6a8
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Franco Bocanegra, Diana, Karina
ad8042ca-0800-495e-a32c-1bdca88aacaa
George, Bethany
41348dd8-14c2-4ec6-a766-9086e1f597d5
Lau, Laurie C.
2af8045d-6162-4939-aba7-28dd2f60f6a8
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Franco Bocanegra, Diana, Karina, George, Bethany, Lau, Laurie C., Holmes, Clive, Nicoll, James A.R. and Boche, Delphine (2019) Microglial motility in Alzheimer’s disease and after aβ42 immunotherapy: a human post-mortem study. Acta Neuropathologica Communications. (doi:10.1186/s40478-019-0828-x).

Record type: Article

Abstract

Microglial function is highly dependent on cell motility, with baseline motility required for homeostatic surveillance activity and directed motility to migrate towards a source of injury. Experimental evidence suggests impaired microglial motility in Alzheimer’s disease (AD) and therefore we have investigated whether the expression of proteins associated with motility is altered in AD and affected by the Aβ immunotherapy using post-mortem brain tissue of 32 controls, 44 AD cases, and 16 AD cases from our unique group of patients immunised against Aβ42 (iAD). Sections of brain were immunolabelled and quantified for (i) the motility-related microglial proteins Iba1, cofilin 1 (CFL1), coronin-1a (CORO1A) and P2RY12, and (ii) pan-Aβ, Aβ42 and phosphorylated tau (ptau). The neuroinflammatory environment was characterised using Meso Scale Discovery multiplex assays. The expression of all four motility-related proteins was unmodified in AD compared with controls, whereas Iba1 and P2RY12, the homeostatic markers, were increased in the iAD group compared with AD. Iba1 and P2RY12 showed significant positive correlations with Aβ in controls but not in the AD or iAD groups. Pro- and anti-inflammatory proteins were increased in AD, whereas immunotherapy appears to result in a slightly less pro-inflammatory environment. Our findings suggest that as Aβ appears during the ageing process, the homeostatic Iba1 and P2RY12 –positive microglia respond to Aβ, but this response is absent in AD. Aβ immunisation promoted increased Iba1 and P2RY12 expression, likely reflecting increased baseline microglial motility but without restoring the profile observed in controls

Text
ANEC_D_19_00388_R1 - Accepted Manuscript
Download (1MB)
Text
document - Version of Record
Available under License Creative Commons Attribution.
Download (4MB)
Text
ANEC-D-19-00388_R1
Restricted to Repository staff only
Request a copy

More information

Accepted/In Press date: 7 October 2019
e-pub ahead of print date: 8 November 2019
Keywords: human microglia, cell motility, Alzheimer’s disease, Aβ immunotherapy, neuroinflammation

Identifiers

Local EPrints ID: 435262
URI: https://eprints.soton.ac.uk/id/eprint/435262
ISSN: 2051-5960
PURE UUID: 1ea8e8da-1df1-43db-b442-797f802b6cf3
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 29 Oct 2019 17:30
Last modified: 07 Dec 2019 05:01

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×