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Innate immunity in Alzheimer's disease: the relevance of animal models?

Innate immunity in Alzheimer's disease: the relevance of animal models?
Innate immunity in Alzheimer's disease: the relevance of animal models?
The mouse is one of the organisms most widely used as an animal model in biomedical research, due to the particular ease with which it can be handled and reproduced in laboratory. As a member of the mammalian class, mice share with humans many features regarding metabolic pathways, cell morphology and anatomy. However, important biological differences between mice and humans exist and must be taken into consideration when interpreting research results, in order to properly translate evidence from experimental studies into information that can be useful for human disease prevention and/or treatment.
With respect to Alzheimer’s disease (AD), much of the experimental information currently known about this disease has been gathered from studies using mainly mice as models. Therefore, it is notably important to fully characterise the differences between mice and humans regarding important aspects of the disease. It is now widely known that inflammation plays an important role in the development of AD, a role that is not only a response to the surrounding pathological environment, but rather seems to be strongly implicated in the aetiology of the disease as indicated by the genetic studies.
This review highlights relevant differences in inflammation and in microglia, the innate immune cell of the brain, between mice and humans regarding genetics and morphology in normal ageing, and the relationship of microglia with AD-like pathology, the inflammatory profile and cognition.
We conclude that, although there are some noteworthy differences exist between mice and humans regarding microglial characteristics, mainly in distribution, and gene expression and states of activation. This may have repercussions in the way transgenic mice respond to, and influence, the AD-like pathology. However, despite these differences, human and mouse microglia also show several similarities in activation patterns, morphology and behaviour such that the mouse is a suitable model for studying the role of microglia in Alzheimer’s disease and other neurodegenerative diseases, as long as these differences are taken into consideration when delineating new strategies to approach the study of neurodegenerative diseases.
0300-9564
20
Franco Bocanegra, Diana K.
ad8042ca-0800-495e-a32c-1bdca88aacaa
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Franco Bocanegra, Diana K.
ad8042ca-0800-495e-a32c-1bdca88aacaa
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Franco Bocanegra, Diana K., Nicoll, James A.R. and Boche, Delphine (2017) Innate immunity in Alzheimer's disease: the relevance of animal models? Journal of Neural Transmission, 20. (doi:10.1007/s00702-017-1729-4).

Record type: Article

Abstract

The mouse is one of the organisms most widely used as an animal model in biomedical research, due to the particular ease with which it can be handled and reproduced in laboratory. As a member of the mammalian class, mice share with humans many features regarding metabolic pathways, cell morphology and anatomy. However, important biological differences between mice and humans exist and must be taken into consideration when interpreting research results, in order to properly translate evidence from experimental studies into information that can be useful for human disease prevention and/or treatment.
With respect to Alzheimer’s disease (AD), much of the experimental information currently known about this disease has been gathered from studies using mainly mice as models. Therefore, it is notably important to fully characterise the differences between mice and humans regarding important aspects of the disease. It is now widely known that inflammation plays an important role in the development of AD, a role that is not only a response to the surrounding pathological environment, but rather seems to be strongly implicated in the aetiology of the disease as indicated by the genetic studies.
This review highlights relevant differences in inflammation and in microglia, the innate immune cell of the brain, between mice and humans regarding genetics and morphology in normal ageing, and the relationship of microglia with AD-like pathology, the inflammatory profile and cognition.
We conclude that, although there are some noteworthy differences exist between mice and humans regarding microglial characteristics, mainly in distribution, and gene expression and states of activation. This may have repercussions in the way transgenic mice respond to, and influence, the AD-like pathology. However, despite these differences, human and mouse microglia also show several similarities in activation patterns, morphology and behaviour such that the mouse is a suitable model for studying the role of microglia in Alzheimer’s disease and other neurodegenerative diseases, as long as these differences are taken into consideration when delineating new strategies to approach the study of neurodegenerative diseases.

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Accepted/In Press date: 27 April 2017
e-pub ahead of print date: 17 May 2017
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 408598
URI: https://eprints.soton.ac.uk/id/eprint/408598
ISSN: 0300-9564
PURE UUID: bfb2d4ec-38de-4502-a4b0-520be7d8bdb9
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

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Date deposited: 25 May 2017 04:02
Last modified: 10 Dec 2019 01:49

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