Cognitive phenotyping of amyloid precursor protein transgenic J20 mice

Karl, Tim; Bhatia, Surabhi; Cheng, David; Kim, Woojin Scott; Garner, Brett

doi:10.1016/j.bbr.2011.12.021

Cited by 42 publications

(37 citation statements)

References 34 publications

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“…Fear conditioning deficits appear consistent with the presentation of spatial working memory and recognition memory deficits in this model (Saura et al, 2005). Interestingly, this model does not appear to display working memory deficits on tasks of alternation such as the Y-maze (Murakami et al, 2011; Karl et al, 2012). …”

Section: Temporal Progression Of the Cognitive Deficits Seen In The Cmentioning

confidence: 94%

“…The asterisk appearing in the age column represents when diffuse amyloid plaques are first observable in the brain for that particular mouse model of AD. The numbers within each cell correspond to the following references: 1: (Games et al, 1995), 2: (Nilsson et al, 2004), 3: (Dodart et al, 1999), 4: (Hartman et al, 2005), 5: (Dodart et al, 2002), 6: (Chen et al, 2000), 7: (Hsiao et al, 1996), 8: (Dineley et al, 2002), 9: (Chapman et al, 1999), 10: (King et al, 1999), 11: (Arendash et al, 2001a), 12: (Arendash et al, 2004), 13: (Ohno et al, 2004), 14: (Yassine et al, 2013), 15: (Westerman et al, 2002), 16: (Corcoran et al, 2002), 17: (Oules et al, 2012), 18: (Lassalle et al, 2008), 19: (Morgan et al, 2000), 20: (Sturchler-Pierrat et al, 1997), 21: (Van Dam et al, 2003), 22: (Huang et al, 2006), 23: (Heneka et al, 2006), 24: (Prut et al, 2007), 25: (Kelly et al, 2003), 26: (Lalonde et al, 2002), 27: (Dumont et al, 2004), 28: (Chishti et al, 2001), 29: (Hyde et al, 2005), 30: (Hanna et al, 2012), 31:(Ambree et al, 2009), 32: (Gortz et al, 2008), 33:(Richter et al, 2008), 34: (Lovasic et al, 2005), 35: (Janus, 2004), 36: (Hanna et al, 2009), 37: (Mucke et al, 2000), 38: (Harris et al, 2010), 39: (Saura et al, 2005), 40: (Simon et al, 2009), 41: (Lustbader et al, 2004), 42: (Cheng et al, 2007), 43: (Cisse et al, 2011), 44: (Du et al, 2011), 45: (Palop et al, 2003), 46: (Murakami et al, 2011), 47: (Escribano et al, 2009), 48: (Fang et al, 2012), 49: (Karl et al, 2012), 50: (Galvan et al, 2006). …”

Section: Temporal Progression Of the Cognitive Deficits Seen In The Cmentioning

confidence: 99%

“…These deficits in recognition memory are present when assessed at several other time points (Escribano et al, 2009; Simon et al, 2009; Cisse et al, 2011). However, they do not appear to progress with the age of the animal and there has even been a report of no recognition memory deficits in old animals in advanced stages of the disease (Karl et al, 2012). Early memory deficits can also be observed in spatial working memory at 3 months of age when assessed by the MWM and the RAWM tasks (Lustbader et al, 2004; Cheng et al, 2007; Meilandt et al, 2008).…”

Section: Temporal Progression Of the Cognitive Deficits Seen In The Cmentioning

confidence: 99%

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Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models

et al. 2014

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The goal of this review is to discuss how behavioral tests in mice relate to the pathological and neuropsychological features seen in human Alzheimer's disease (AD), and present a comprehensive analysis of the temporal progression of behavioral impairments in commonly used AD mouse models that contain mutations in amyloid precursor protein (APP). We begin with a brief overview of the neuropathological changes seen in the AD brain and an outline of some of the clinical neuropsychological assessments used to measure cognitive deficits associated with the disease. This is followed by a critical assessment of behavioral tasks that are used in AD mice to model the cognitive changes seen in the human disease. Behavioral tests discussed include spatial memory tests [Morris water maze (MWM), radial arm water maze (RAWM), Barnes maze], associative learning tasks (passive avoidance, fear conditioning), alternation tasks (Y-Maze/T-Maze), recognition memory tasks (Novel Object Recognition), attentional tasks (3 and 5 choice serial reaction time), set-shifting tasks, and reversal learning tasks. We discuss the strengths and weaknesses of each of these behavioral tasks, and how they may correlate with clinical assessments in humans. Finally, the temporal progression of both cognitive and non-cognitive deficits in 10 AD mouse models (PDAPP, TG2576, APP23, TgCRND8, J20, APP/PS1, TG2576 + PS1 (M146L), APP/PS1 KI, 5×FAD, and 3×Tg-AD) are discussed in detail. Mouse models of AD and the behavioral tasks used in conjunction with those models are immensely important in contributing to our knowledge of disease progression and are a useful tool to study AD pathophysiology and the resulting cognitive deficits. However, investigators need to be aware of the potential weaknesses of the available preclinical models in terms of their ability to model cognitive changes observed in human AD. It is our hope that this review will assist investigators in selecting an appropriate mouse model, and accompanying behavioral paradigms to investigate different aspects of AD pathology and disease progression.

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Section: Temporal Progression Of the Cognitive Deficits Seen In The Cmentioning

confidence: 94%

Section: Temporal Progression Of the Cognitive Deficits Seen In The Cmentioning

confidence: 99%

Section: Temporal Progression Of the Cognitive Deficits Seen In The Cmentioning

confidence: 99%

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Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models

et al. 2014

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“…Moreover, no prior published study directly tested the effects of m266 versus another anti-Aβ antibody, nor assessed the effect of treatment on cerebral Aβ oligomers. Here we tested m266 alongside a recently described aggregate-preferring antibody, 1C22 (O’Nuallain et al, 2014; Yang et al, 2015) employing the well-characterized J20 mouse model (Cheng et al, 2007; Chin et al, 2005; Karl et al, 2012; Mably et al, 2015; Palop et al, 2003; Roberson et al, 2011; Roberson et al, 2007; Wright et al, 2013). The J20 model was chosen because it has important similarities to the PDAPP mouse model which is the only model in which m266 has ever been tested.…”

Section: Introductionmentioning

confidence: 99%

Anti-Aβ antibodies incapable of reducing cerebral Aβ oligomers fail to attenuate spatial reference memory deficits in J20 mice

Mably

Donald

et al. 2015

Neurobiology of Disease

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Compelling genetic evidence links the amyloid precursor protein (APP) to Alzheimer’s disease (AD). A leading hypothesis proposes that a small amphipathic fragment of APP, the amyloid β-protein (Aβ), self-associates to form soluble assemblies loosely referred to as “oligomers” and that these are primary mediators of synaptic dysfunction. As such, Aβ, and specifically Aβ oligomers, are targets for disease modifying therapies. Currently, the most advanced experimental treatment for AD relies on the use of anti-Aβ antibodies. In this study, we tested the ability of the monomer-preferring antibody, m266 and a novel aggregate-preferring antibody, 1C22, to attenuate spatial reference memory impairments in J20 mice. Chronic treatment with m266 resulted in a ~70-fold increase in Aβ detected in the bloodstream, and a ~50% increase in water-soluble brain Aβ – and in both cases Aβ was bound to m266. In contrast, 1C22 increased the levels of free Aβ in the bloodstream, and bound to amyloid deposits in J20 brain. However, neither 1C22 nor m266 attenuated the cognitive deficits evident in 12 month old J20 mice. Moreover, both antibodies failed to alter the levels of soluble Aβ oligomers in J20 brain. These results suggest that Aβ oligomers may mediate the behavioral deficits seen in J20 mice and highlight the need for the development of aggregate-preferring antibodies that can reach the brain in sufficient levels to neutralize bioactive Aβ oligomers. Aside from the lack of positive effect of m266 and 1C22 on cognition a substantial number of deaths occurred in m266- and 1C22-immunized J20 mice. These fatalities were specific to anti-Aβ antibodies and to the J20 mouse line since treatment of wild type or PDAPP mice with these antibodies did not cause any deaths. These and other recent results indicate that J20 mice are particularly susceptible to targeting of the APP/Aβ/tau axis. Notwithstanding the specificity of fatalities for J20 mice, it is worrying that the murine precursor (m266) of a lead experimental therapeutic, Solanezumab, did not engage with putatively pathogenic Aβ oligomers.

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“…Indeed, both MCI-AD patients and hAPP mice showed poorer hidden target and probe trial per formance. In contrast to MCI-AD patients, however, hAPP mice exhibited deficits in visible platform testing, as reported incon sistently before (18)(19)(20). Possin and col leagues attributed the learning deficit to difficulty in relinquishing a thigmotactic Figure 1.…”

Section: Discussionmentioning

confidence: 79%

Wet or dry: translatable “water mazes” for mice and humans

Higa¹,

Young²,

Geyer³

2016

Journal of Clinical Investigation

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C o m m e n t a r y4A disconnect between animal models and human AD patientsAlzheimer's disease (AD) is a devastating illness and the leading cause of dementia in older adults. As with other neurological disorders, the study of AD relies on ani mal models in conjunction with human studies to explore the pathogenesis of the disease and to develop treatments to slow or prevent disease progression. Thus far, treatments with agents such as acetylcho linesterase (AChE) inhibitors to alleviate the cognitive deficits associated with AD produce only modest cognitive improve ments that are neither permanent nor preventative of further decline (1, 2). To better predict the efficacy of therapeutic strategies, it is necessary to develop trans latable paradigms that reliably model cognitive impairment (and improvement) across species, as discussed for other diseases with cognitive deficits such as schizophrenia (3, 4). The pathogenesis and biological sig natures of AD are well established, and several mouse lines have been developed to mimic β amyloid plaque and tau neuro fibrillary tangle formation (5, 6). These models often exhibit cognitive deficits similar to those observed in patients at various stages of AD. Directly translat able comparisons are limited, however, because rodents are assessed with etho logically relevant tasks, while patients are tested using pen and paper.For rodents, the most commonly used test of spatial learning and memory is the Morris water maze (MWM). There are several versions of the MWM designed to assess various elements of spatial learning and memory, and several mouse models of AD exhibit impaired performance in the MWM. Classic human tests rely more on memory tests that are based on short stories or visual image reproductions (5). Recently, the MWM has been reverse translated for use in humans, providing evi dence that patients with AD are impaired in twodimensional, real space, and virtual reality versions of the task (7-10).Although performance in the MWM of both mice and humans relies on hippo campal integrity (7, 11), especially the right hippocampus for AD patients (12), the extent to which rodent MWM performance can predict and be compared with human performance was heretofore unknown. In this issue, Possin et al. (13) assessed the translatability of MWM findings by using comparable mouse and human MWM para digms and measures (Table 1 and Figure 1), enabling direct comparisons across species. Performance comparison of species-specific MWM paradigmsBoth mouse and human versions had three test stages: visible target training, hidden target learning, and a probe test. The human test took place in a virtual cir cular field that was navigable with a steer ing wheel. This methodology enabled firstperson exploration of the space to find a reward. Mice, however, had to navigate through water to find first the visible, then hidden escape platforms. The performance measures analyzed for the visible and hid den target stages were distance (mean proximity to the target), latency (percent age of ...

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Cognitive phenotyping of amyloid precursor protein transgenic J20 mice

Cited by 42 publications

References 34 publications

Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models

Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models

Anti-Aβ antibodies incapable of reducing cerebral Aβ oligomers fail to attenuate spatial reference memory deficits in J20 mice

Wet or dry: translatable “water mazes” for mice and humans

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