Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease

Wirths, Oliver; Breyhan, Henning; Schäfer, S; Roth, Christian; Bayer, Thomas A.

doi:10.1016/j.neurobiolaging.2006.12.004

Cited by 78 publications

(68 citation statements)

References 52 publications

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“…In addition, a possible toxic effect of soluble Ab species is likely to be negligible, because other groups of neurons like dentate gyrus granule cells, which do not accumulate intraneuronal Ab are unaffected. Previously, we also have shown that (a) 85% of total Ab in APP/PS1KI mice consist of Ab42, (b) that 1-year-old mice exhibit a 50% CA1 neuron loss [2], and (c) that robust learning deficits occur already at 6 months of age [46].…”

Section: Discussionmentioning

confidence: 64%

“…This is the only mouse model so far, developing abundant hippocampal neuron loss at the age of 1 year [2]. We have shown previously that these mice exhibit severe and early learning deficits at the age of 6 months [46]. This observation prompted us to study the basis of these early learning deficits using anatomical and physiological techniques in more detail in the present report.…”

Section: Introductionmentioning

confidence: 78%

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APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy

et al. 2009

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Abeta accumulation has an important function in the etiology of Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and changes in personality. However, the mode of this toxic activity is still a matter of scientific debate. We used the APP/PS1KI mouse model for AD, because it is the only model so far which develops 50% hippocampal CA1 neuron loss at the age of 1 year. Previously, we have shown that this model develops severe learning deficits occurring much earlier at the age of 6 months. This observation prompted us to study the anatomical and cellular basis at this time point in more detail. In the current report, we observed that at 6 months of age there is already a 33% CA1 neuron loss and an 18% atrophy of the hippocampus, together with a drastic reduction of long-term potentiation and disrupted paired pulse facilitation. Interestingly, at 4 months of age, there was no long-term potentiation deficit in CA1. This was accompanied by reduced levels of pre-and post-synaptic markers. We also observed that intraneuronal and total amount of different Abeta peptides including N-modified, fibrillar and oligomeric Abeta species increased and coincided well with CA1 neuron loss. Overall, these data provide the basis for the observed robust working memory deficits in this mouse model for AD at 6 months of age.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 78%

APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy

et al. 2009

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“…The balance beam, cross-maze, and elevated plus maze (EPM) were performed as described previously (24,25). For the cross-maze, spontaneous alternation rates were calculated as the percentage of actual alternations made relative to the total number of possible alternations.…”

Section: Methodsmentioning

confidence: 99%

Pyroglutamate Amyloid β (Aβ) Aggravates Behavioral Deficits in Transgenic Amyloid Mouse Model for Alzheimer Disease

Wittnam

Portelius

Zetterberg

et al. 2012

Journal of Biological Chemistry

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“…Accumulation of Ab in cells and parenchyma is a characteristic of TBI, and has been suggested to be an early event in AD pathology, preceding the development of mature amyloid plaques (Gomez-Ramos and Asuncion Moran, 2007;LaFerla et al, 2007;Wirths et al, 2008). To assess whether APOE polymorphisms modified intracellular Ab accumulation after TBI, animals were sacrificed at 1, 2, 4, and 12 weeks after TBI and brain slices were immunostained with 4G8 (antibody against Ab).…”

Section: Fig 1 Total Ab Levels Increase Post-tbi (A) Total and (B)mentioning

confidence: 99%

Traumatic Brain Injury Exacerbates Neurodegenerative Pathology: Improvement with an Apolipoprotein E-Based Therapeutic

Laskowitz

Song

Wang

et al. 2010

Journal of Neurotrauma

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Cognitive impairment is common following traumatic brain injury (TBI), and neuroinflammatory mechanisms may predispose to the development of neurodegenerative disease. Apolipoprotein E (apoE) polymorphisms modify neuroinflammatory responses, and influence both outcome from acute brain injury and the risk of developing neurodegenerative disease. We demonstrate that TBI accelerates neurodegenerative pathology in double-transgenic animals expressing the common human apoE alleles and mutated amyloid precursor protein, and that pathology is exacerbated in the presence of the apoE4 allele. The administration of an apoE-mimetic peptide markedly reduced the development of neurodegenerative pathology in mice homozygous for apoE3 as well as apoE3/E4 heterozygotes. These results demonstrate that TBI accelerates the cardinal neuropathological features of neurodegenerative disease, and establishes the potential for apoE mimetic therapies in reducing pathology associated with neurodegeneration.

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Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease

Cited by 78 publications

References 52 publications

APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy

APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy

Pyroglutamate Amyloid β (Aβ) Aggravates Behavioral Deficits in Transgenic Amyloid Mouse Model for Alzheimer Disease

Traumatic Brain Injury Exacerbates Neurodegenerative Pathology: Improvement with an Apolipoprotein E-Based Therapeutic

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