P2–382: Tg4–42: A new mouse model of Alzheimer's disease—N‐truncated amyloid β (Aβ) 4–42 induces severe neuron loss and behavioral deficits

Bouter, Yvonne; Dietrich, Katharina; Wittnam, Jessica L.; Pillot, Thierry; Papot-Couturier, Sophie; Lefebvre, Thomas; Sprenger, Frederick; Wirths, Oliver; Bayer, Thomas A.

doi:10.1016/j.jalz.2013.05.1031

Cited by 1 publication

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“…Nevertheless, Tg4-42 mice did not show any impairments in the Open Field that could possibly influence anxiety- and memory-related behavior. In line with these findings, general motor abilities of Tg4-42 mice have been shown to be intact in the Morris water maze as swimming speed did not differ from wild-type animals (Bouter et al, 2013, 2014, 2019; Antonios et al, 2015).…”

Section: Discussionsupporting

confidence: 70%

“…In previous studies we could show a severe learning deficit in the Morris water maze, beginning from the age of 5 months in Tg4-42 mice (Antonios et al, 2015). Interestingly, despite the massive impairments in the rotarod, the ability to swim in the Morris water maze was not altered in same-aged Tg4-42 mice (Bouter et al, 2013, 2014; Antonios et al, 2015).…”

Section: Discussionmentioning

confidence: 95%

“…The generation of Tg4-42 mice has been described previously (Bouter et al, 2013). Briefly, Tg4-42 mice express human Aβ4-42 fused to the murine thyrotropin releasing hormone signal peptide under the control of the neuronal Thy-1 promoter.…”

Section: Methodsmentioning

confidence: 99%

“…Among the different species, Aβ beginning with phenylalanine at position 4 is particularly abundant in the brain of AD patients (Masters et al, 1985; Portelius et al, 2010). The transgenic mouse model Tg4-42 expresses exclusively intraneuronal Aβ4-42 without human amyloid precursor protein (APP) overexpression (Bouter et al, 2013). Intracellular Aβ accumulation is accompanied by micro- and astrogliosis that is most abundant in the hippocampus of these mice.…”

Section: Introductionmentioning

confidence: 99%

“…Tg4-42 mice develop severe synaptic impairments and neuron loss especially in the CA1 region of the hippocampus. Furthermore, Tg4-42 mice develop age-dependent behavior and memory deficits albeit without plaque formation (Bouter et al, 2013, 2019; Dietrich et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Motor Function in the Tg4-42 Mouse Model of Alzheimer’s Disease

Wagner

Sichler

Schleicher

et al. 2019

Front. Behav. Neurosci.

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Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. Hallmarks of AD are memory impairments and cognitive deficits, but non-cognitive impairments, especially motor dysfunctions are also associated with the disease and may even precede classic clinical symptoms. With an aging society and increasing hospitalization of the elderly, motor deficits are of major interest to improve independent activities in daily living. Consistent with clinical findings, a variety of AD mouse models develop motor deficits as well. We investigated the motor function of 3- and 7-month-old Tg4-42 mice in comparison to wild-type controls and 5XFAD mice and discuss the results in context with several other AD mouse model. Our study shows impaired balance and motor coordination in aged Tg4-42 mice in the balance beam and rotarod test, while general locomotor activity and muscle strength is not impaired at 7 months. The cerebellum is a major player in the regulation and coordination of balance and locomotion through practice. Particularly, the rotarod test is able to detect cerebellar deficits. Furthermore, supposed cerebellar impairment was verified by 18 F-FDG PET/MRI. Aged Tg4-42 mice showed reduced cerebellar glucose metabolism in the 18 F-FDG PET. Suggesting that, deficits in coordination and balance are most likely due to cerebellar impairment. In conclusion, Tg4-42 mice develop motor deficits before memory deficits, without confounding memory test. Thus, making the Tg4-42 mouse model a good model to study the effects on cognitive decline of therapies targeting motor impairments.

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