Old cats : a naturally occuring model of tauopathy.
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1
Free University of Brussels, Belgium
Tauopathies comprise several neurodegenerative diseases such as Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia linked to chromosome 17 and Pick’s disease. These diseases have in common the presence of a cerebral lesion composed of abnormally phosphorylated and aggregated tau proteins forming filaments.
In humans, 6 isoforms of tau proteins are expressed in the adult brain. These isoforms differ by the presence or absence of 1 or 2 inserts in the N terminal part of the protein (0N, 1N, 2N) and by the presence of 3 or 4 semi-repetitive microtubule binding domains in the C-terminal part of the protein (3R or 4R) (Isoforms called 0N3R, 1N3R, 2N3R, 0N4R, 1N4R, 2N4R). In cats, 5 isoforms are expressed in the brain of adult cats (0N3R, 2N3R, 0N4R, 1N4R, 2N4R). In Alzheimer’s disease, all the 6 isoforms of tau are found in neurofibrillary tangles of Alzheimer’s disease subjects whereas in progressive supranuclear palsy, corticobasal degeneration and some frontotemporal dementia, aggregated tau proteins are mainly composed of 4R isoforms. In Pick’s disease, the Pick bodies are mainly constituted of 3R tau.
Previous studies have shown that phosphorylated tau proteins can form aggregates in mammalian species such as cats, goats or cynomolgus monkeys (Nelson et al. 1994 ; Oikawa et al., 2010 ; Chambers et al., 2015 ; Uchihara et al., 2016) but only in the presence of amyloid deposits in the cats (Chambers et al., 2015). In this study, we will show for the first time that a tau pathology could develop without the presence of amyloid deposits in old cats.
We analyzed the brain of a cohort of cats between 2 and 21 years old for the presence of a tau pathology. Such a pathology was not found in cats younger than 18 years. In 3 among 5 cats aged between 18 and 21 years, we observed an accumulation of phosphorylated and aggregated tau in neuronal cell bodies and in oligodendrocytes. These tau aggregates were ubiquitin, PHF1, AT8, Gallyas, thioflavin, and thiazin red positive and were mainly composed of 4R tau isoforms. They were observed in the hippocampus and the adjacent cortex in these three cats, in the caudate putamen in two cats and even in the brain stem in one cat. Amyloid deposits were not detected in any of these 3 aged cats. The presence of hyperphosphorylated tau was confirmed by western blotting on the lysates from frontal cortex of these 3 cats. Phosphorylated tau are sarkosyl insoluble and forms straight filaments (observed by electron microscopy).
In conclusion, we here document the existence of a naturally occurring 4R primary tauopathy in the feline species, associated with aging and independent of Aß deposits. This observation supports the hypothesis that tau and Aß pathologies develop initially independently in several mammalian species, in neurodegenerative diseases.
References
Chambers JK, Tokuda T, Uchida K, Ishii R, Tatebe H, Takahashi E, Tomiyama T, Une Y, Nakayama H. The domestic cat as a natural animal model of Alzheimer's disease. Acta Neuropathol Commun. 2015 Dec 10;3:78.
Nelson PT, Greenberg SG, Saper CB. Neurofibrillary tangles in the cerebral cortex of sheep. Neurosci Lett. 1994 Mar 28;170(1):187-90.
Oikawa N, Kimura N, Yanagisawa K. Alzheimer-type tau pathology in advanced aged nonhuman primate brains harboring substantial amyloid deposition. Brain Res. 2010 Feb 22;1315:137-49.
Uchihara T, Endo K, Kondo H, Okabayashi S, Shimozawa N, Yasutomi Y, Adachi E, Kimura N. Tau pathology in aged cynomolgus monkeys is progressive supranuclear palsy/corticobasal degeneration- but not Alzheimer disease-like -Ultrastructural mapping of tau by EDX. Acta Neuropathol Commun. 2016 Nov 14;4(1):118.
Keywords:
Tauopathy,
tau,
cat,
Alzheimer,
progressive supra nuclear palsy,
Amyloid,
Neurofibrillary Tangles,
Old cats
Conference:
Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018.
Presentation Type:
e-posters
Topic:
NOVEL STRATEGIES FOR NEUROLOGICAL AND MENTAL DISORDERS: SCIENTIFIC BASIS AND VALUE FOR PATIENT-CENTERED CARE
Citation:
Poncelet
L,
Ando
K,
Vergara
C,
Gilissen
EP,
Brion
J and
Leroy
K
(2019). Old cats : a naturally occuring model of tauopathy..
Front. Neurosci.
Conference Abstract:
Belgian Brain Congress 2018 — Belgian Brain Council.
doi: 10.3389/conf.fnins.2018.95.00007
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Received:
08 Aug 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Prof. Karelle Leroy, Free University of Brussels, Brussels, Belgium, kleroy@ulb.ac.be