Strain specific differences in memory and neuropathology in a mouse model of Alzheimer's disease

Glazner, Kathryn A. C.; Odero, Gary; Anema, Everet; Motnenko, Anna; Schapansky, Jason; Grossman, Denise; Oliver, Derek R.; Glazner, Gordon W.; Albensi, Benedict C.

doi:10.1016/j.lfs.2010.04.014

Cited by 23 publications

(19 citation statements)

References 25 publications

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“…For example, crossing to a 129 strain masks cognitive deficits that were apparent on a 129–C57BL/6 mixed background [179]. Similarly, the TgCRND8 line has a more severe phenotype in the Morris water maze and significantly higher plaque deposition on a 129–C57BL/6 mixed background than on a C3H–C57BL/6 mixed background [54]. Finally, the same hAPP transgene produces a more severe phenotype on the FVB/N background than on a mixed C57BL/6–SJL background [74].…”

Section: Genetic Mouse Models Of Admentioning

confidence: 99%

Mouse models of Alzheimer's disease

Hall

Roberson

2012

Brain Research Bulletin

261

208

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Alzheimer’s disease (AD) is the most common cause of dementia, affecting 35 million people today. The search for new treatments is made ever more urgent by prospects for increasing prevalence due to population aging. Mouse models are one of the most important research tools for finding new treatments for AD. Here, we review those models. We begin by briefly reviewing the AD genetics on which mouse models are based and then consider the most common mouse models of AD, including mice transgenic for human amyloid precursor protein (hAPP) and beta-amyloid (Aβ), mice expressing mutant presenilin genes, mice modeling tau’s role in AD, and apolipoprotein E models. The discussion highlights key features and important differences between these mouse models. We conclude with a discussion about the role of AD mouse models in the translational pipeline.

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Section: Genetic Mouse Models Of Admentioning

confidence: 99%

Mouse models of Alzheimer's disease

Hall

Roberson

2012

Brain Research Bulletin

261

208

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“…However, these deficits vary in magnitude and time of onset, vary according to background strain (Glazner et al . 2010) and have not been reported by all laboratories (King and Arendash 2002). A recent meta-analysis of multiple studies with Tg2576 reported that when performance of control animals expressing human APP without the Swedish mutation is taken into account, this effect only becomes apparent between 12 and 18 months and requires large numbers of animals (Reed et al .…”

Section: Interogating the Key Determinants Of Cognitive Dysfunction Imentioning

confidence: 81%

Non-Steroidal Anti-Inflammatory Drugs and Cognitive Function: Are Prostaglandins at the Heart of Cognitive Impairment in Dementia and Delirium ?

Cunningham

Skelly

2011

J Neuroimmune Pharmacol

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Studies of non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis imply that inflammation is important in the development of Alzheimer’s disease (AD). However, these drugs have not alleviated the symptoms of AD in those who have already developed dementia. This suggests that the primary mediator targeted by these drugs, PGE2, is not actively suppressing memory function in AD. Amyloid-β oligomers appear to be important for the mild cognitive changes seen in AD transgenic mice, yet amyloid immunotherapy has also proven unsuccessful in clinical trials. Collectively, these findings indicate that NSAIDs may target a prodromal process in mice that has already passed in those diagnosed with AD, and that synaptic and neuronal loss are key determinants of cognitive dysfunction in AD. While the role of inflammation has not yet become clear, inflammatory processes definitely have a negative impact on cognitive function during episodes of delirium during dementia. Delirium is an acute and profound impairment of cognitive function frequently occurring in aged and demented patients exposed to systemic inflammatory insults, which is now recognised to contribute to long-term cognitive decline. Recent work in animal models is beginning to shed light on the interactions between systemic inflammation and CNS pathology in these acute exacerbations of dementia. This review will assess the role of prostaglandin synthesis in the memory impairments observed in dementia and delirium and will examine the relative contribution of amyloid, synaptic and neuronal loss. We will also discuss how understanding the role of inflammatory mediators in delirious episodes will have major implications for ameliorating the rate of decline in the demented population.

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“…Additionally, inbred C57BL/6 AβPP transgenic mice have higher amyloid plaque deposition than AβPP transgenic mice of either an A/J or a mixed C57BL/6 × DBA/2 genetic background (Ozmen et al, 2007; Sebastiani et al, 2006). Strain background has also been shown to have a strong influence on the performance of AβPP transgenic mice in a variety of behavioral assays (Glazner et al, 2010; Lassalle et al, 2008; Rustay et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice

Couch

Kerrisk

Kaufman

et al. 2013

J of Comparative Neurology

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Alzheimer’s disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4–9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment is delayed considerably in outcrossed AβPP/PS1 mice relative to inbred mice on a C57BL/6 background. While inbred AβPP/PS1 mice develop deficits in radial-arm water maze performance and novel object recognition as early as 8 months, outcrossed AβPP/PS1 mice do not display defects until 18 months. Within the forebrain, we find that inbred AβPP/PS1 mice have significantly higher amyloid plaque burden at 12 months than outcrossed AβPP/PS1 mice of the same age. Surprisingly, inbred AβPP/PS1 mice at 8 months have low plaque burden suggesting that plaque burden alone cannot explain the accompanying behavioral deficits. Analysis of AβPP processing revealed that elevated levels of soluble Aβ correlate with the degree of behavioral impairment in both strains. Taken together, these findings suggest that animal behavior, amyloid plaque deposition, and AβPP processing are sensitive to genetic differences between mouse strains.

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Strain specific differences in memory and neuropathology in a mouse model of Alzheimer's disease

Cited by 23 publications

References 25 publications

Mouse models of Alzheimer's disease

Mouse models of Alzheimer's disease

Non-Steroidal Anti-Inflammatory Drugs and Cognitive Function: Are Prostaglandins at the Heart of Cognitive Impairment in Dementia and Delirium ?

Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice

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