PMID- 37895469
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231030
IS  - 2075-1729 (Print)
IS  - 2075-1729 (Electronic)
IS  - 2075-1729 (Linking)
VI  - 13
IP  - 10
DP  - 2023 Oct 20
TI  - Behavioral and Neuropathological Phenotyping of the Tau58/2 and Tau58/4 
      Transgenic Mouse Models for FTDP-17.
LID - 10.3390/life13102088 [doi]
LID - 2088
AB  - BACKGROUND: The Tau58/2 and Tau58/4 mouse lines expressing 0N4R tau with a P301S 
      mutation mimic aspects of frontotemporal dementia and parkinsonism linked to 
      chromosome 17 (FTDP-17). In a side-by-side comparison, we report the 
      age-dependent development of cognitive, motor, and behavioral deficits in 
      comparison with the spatial-temporal evolution of cellular tau pathology in both 
      models. METHODS: We applied the SHIRPA primary screen and specific neuromotor, 
      behavioral, and cognitive paradigms. The spatiotemporal development of tau 
      pathology was investigated immunohistochemically. Levels of sarkosyl-insoluble 
      paired helical filaments were determined via a MesoScale Discovery biomarker 
      assay. RESULTS: Neuromotor impairments developed from age 3 months in both 
      models. On electron microscopy, spinal cord neurofibrillary pathology was visible 
      in mice aged 3 months; however, AT8 immunoreactivity was not yet observed in 
      Tau58/4 mice. Behavioral abnormalities and memory deficits occurred at a later 
      stage (>9 months) when tau pathology was fully disseminated throughout the brain. 
      Spatiotemporally, tau pathology spread from the spinal cord via the midbrain to 
      the frontal cortex, while the hippocampus was relatively spared, thus explaining 
      the late onset of cognitive deficits. CONCLUSIONS: Our findings indicate the face 
      and construct validity of both Tau58 models, which may provide new, valuable 
      insights into the pathologic effects of tau species in vivo and may consequently 
      facilitate the development of new therapeutic targets to delay or halt 
      neurodegenerative processes occurring in tauopathies.
FAU - Van Dam, Debby
AU  - Van Dam D
AUID- ORCID: 0000-0003-4739-6076
AD  - Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, 
      University of Antwerp, Wilrijk, 2610 Antwerp, Belgium.
AD  - Department of Neurology and Alzheimer Center Groningen, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
FAU - Valkenburg, Femke
AU  - Valkenburg F
AD  - Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, 
      University of Antwerp, Wilrijk, 2610 Antwerp, Belgium.
FAU - Van Kolen, Kristof
AU  - Van Kolen K
AD  - Neuroscience Department, Janssen Research and Development, 2340 Beerse, Belgium.
FAU - Pintelon, Isabel
AU  - Pintelon I
AD  - Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, 
      University of Antwerp, 2610 Antwerp, Belgium.
FAU - Timmermans, Jean-Pierre
AU  - Timmermans JP
AUID- ORCID: 0000-0003-2506-6252
AD  - Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, 
      University of Antwerp, 2610 Antwerp, Belgium.
FAU - De Deyn, Peter Paul
AU  - De Deyn PP
AUID- ORCID: 0000-0002-2228-2964
AD  - Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, 
      University of Antwerp, Wilrijk, 2610 Antwerp, Belgium.
AD  - Department of Neurology and Alzheimer Center Groningen, University Medical Center 
      Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
LA  - eng
GR  - n/a/Research Foundation-Flanders/
GR  - n/a/Medical Research Foundation Antwerp/
GR  - n/a/Thomas Riellaerts research fund/
GR  - n/a/Neurosearch Antwerp/
GR  - n/a/Belgian Alzheimer Research Foundation (SAO-FRA)/
GR  - n/a/University of Antwerp/
GR  - n/a/University Medical Center Groningen/
PT  - Journal Article
DEP - 20231020
PL  - Switzerland
TA  - Life (Basel)
JT  - Life (Basel, Switzerland)
JID - 101580444
PMC - PMC10608666
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Morris water maze
OT  - behavioral disinhibition
OT  - cognitive deficits
OT  - frontotemporal dementia
OT  - motor dysfunction
OT  - tauopathy
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/28 11:46
MHDA- 2023/10/28 11:47
PMCR- 2023/10/20
CRDT- 2023/10/28 01:21
PHST- 2023/07/24 00:00 [received]
PHST- 2023/10/10 00:00 [revised]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2023/10/28 11:47 [medline]
PHST- 2023/10/28 11:46 [pubmed]
PHST- 2023/10/28 01:21 [entrez]
PHST- 2023/10/20 00:00 [pmc-release]
AID - life13102088 [pii]
AID - life-13-02088 [pii]
AID - 10.3390/life13102088 [doi]
PST - epublish
SO  - Life (Basel). 2023 Oct 20;13(10):2088. doi: 10.3390/life13102088.