Mouse models of frontotemporal dementia: A comparison of phenotypes with clinical symptomatology

Rebekah M Ahmed; Muireann Irish; Janet van Eersel; Arne Ittner; Yazi D Ke; Alexander Volkerling; Julia van der Hoven; Kimi Tanaka; Tim Karl; Michael Kassiou; Jillian J Kril; Olivier Piguet; Jürgen Götz; Matthew C Kiernan; Glenda M Halliday; John R Hodges; Lars M Ittner

doi:10.1016/j.neubiorev.2017.01.004

Mouse models of frontotemporal dementia: A comparison of phenotypes with clinical symptomatology

Neurosci Biobehav Rev. 2017 Mar;74(Pt A):126-138. doi: 10.1016/j.neubiorev.2017.01.004. Epub 2017 Jan 11.

Authors

Rebekah M Ahmed¹, Muireann Irish², Janet van Eersel³, Arne Ittner³, Yazi D Ke³, Alexander Volkerling³, Julia van der Hoven³, Kimi Tanaka³, Tim Karl⁴, Michael Kassiou⁵, Jillian J Kril⁶, Olivier Piguet⁷, Jürgen Götz⁸, Matthew C Kiernan⁹, Glenda M Halliday¹⁰, John R Hodges¹¹, Lars M Ittner¹²

Affiliations

¹ Neuroscience Research Australia, Sydney, Australia; ARC Centre of Excellence in Cognition and its Disorders, the University of New South Wales, Sydney, Australia; Sydney Medical School, Brain & Mind Centre, University of Sydney, Australia.
² Neuroscience Research Australia, Sydney, Australia; ARC Centre of Excellence in Cognition and its Disorders, the University of New South Wales, Sydney, Australia; School of Psychology, the University of New South Wales, Sydney, Australia; Brain and Mind Centre, University of Sydney, Australia.
³ Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁴ Neuroscience Research Australia, Sydney, Australia.
⁵ Faculty of Health Sciences, The University of Sydney, Australia.
⁶ Discipline of Pathology, Sydney Medical School, The University of Sydney, Australia.
⁷ Neuroscience Research Australia, Sydney, Australia; ARC Centre of Excellence in Cognition and its Disorders, the University of New South Wales, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia; Brain and Mind Centre, University of Sydney, Australia.
⁸ Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
⁹ Sydney Medical School, Brain & Mind Centre, University of Sydney, Australia.
¹⁰ Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia; Brain and Mind Centre, University of Sydney, Australia.
¹¹ Neuroscience Research Australia, Sydney, Australia; ARC Centre of Excellence in Cognition and its Disorders, the University of New South Wales, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia; Brain and Mind Centre, University of Sydney, Australia. Electronic address: john.hodges@sydney.edu.au.
¹² Neuroscience Research Australia, Sydney, Australia; Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia. Electronic address: l.ittner@unsw.edu.au.

PMID: 28088537
DOI: 10.1016/j.neubiorev.2017.01.004

Abstract

Frontotemporal dementia (FTD) is the second most common cause of young onset dementia. It is increasingly recognized that there is a clinical continuum between FTD and amyotrophic lateral sclerosis (ALS). At a clinical, pathological and genetic level there is much heterogeneity in FTD, meaning that our understanding of this condition, pathophysiology and development of treatments has been limited. A number of mouse models focusing predominantly on recapitulating neuropathological and molecular changes of disease have been developed, with most transgenic lines expressing a single specific protein or genetic mutation. Together with the species-typical presentation of functional deficits, this makes the direct translation of results from these models to humans difficult. However, understanding the phenotypical presentations in mice and how they relate to clinical symptomology in humans is essential for advancing translation. Here we review current mouse models in FTD and compare their phenotype to the clinical presentation in patients.

Keywords: Amyotrophic lateral sclerosis; Behavioural neurology; Frontotemporal dementia; Mouse; Transgenic.

Publication types

Review

MeSH terms

Amyotrophic Lateral Sclerosis
Animals
Disease Models, Animal
Frontotemporal Dementia*
Humans
Mice
Mutation
Phenotype