Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice

Hyde, Lynn A.; Kazdoba, Tatiana M.; Grilli, Mariagrazia; Lozza, Gianluca; Brussa, Rosella; Zhang, Qi; Wong, George S. K.; McCool, Martha F.; Zhang, Lili; Parker, Eric M.; Higgins, Guy A.

doi:10.1016/j.bbr.2004.12.017

Cited by 68 publications

(70 citation statements)

References 33 publications

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“…Elevated BLI signals in the Tg(CRND8:Gfapluc) mice were apparent at 7 mo of age. Using the Morris water maze, Tg(CRND8) mice showed delayed escape latency at ∼5 mo, but impaired performance in the probe trail was not evident until 9-10 mo of age (31). Delayed escape latency in the Morris water maze was reported in Tg(APP23) mice at 17-25 mo of age (23), whereas elevated BLI signals occurred in Tg(APP23:Gfapluc) mice at ∼14 mo of age.…”

Section: Comparison Between Bli and Other Techniques Used For Assessingmentioning

confidence: 94%

Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease

Watts

Giles

Grillo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

105

109

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The undersigned authors wish to note, "The KefFC system of E. coli is maintained in an inactive state by the binding of glutathione (GSH) and is activated by the formation of GSH adducts (GSX), particularly those with bulky substituents. We described two crystal structures with density present in the ligand-binding domain that we interpreted as GSH and GSX. Recently, an independent, experienced crystallographer, who had viewed the structures from our study in a different context, made representations to us that cast doubt on position of the succinimido ring of GSX. We have further reviewed the density maps with the aid of an experienced crystallographer. As a consequence, we believe it is important to draw this altered interpretation of the crystal structures to the attention of readers. In both structures, the density for the backbone of GSH is clear and allows unequivocal assignment of the position of the tripeptide. In PDB coordinate set 3L9X, the density for the succinimido ring is very weak, making interpretation very speculative and the assignment rests on the identity of the ligand added to the crystallization mixture, for which there are two diastereomers in the solutiona possibility that provides some basis for weakening the density. However, in 3L9W there are two anomalies that affect the interpretation of the bound ligand. First, there is no density for the carbon atom attached to the sulfur of GSH and second, there is extra density adjacent to the position of sulfur that could be modelled as a constrained succinimido ring. However, this density could also be water or any other molecule that is trapped in the structure. Thus, while there is good evidence for the peptide, the evidence that it is in the GSH form is uncertain."There are no new data on either the structures or on the gating mechanism. However, we believe that we should be cautious in interpreting the structural data and that the field in general should be made aware of the alternative views of the electron density data. Note that the mutagenesis and spectroscopic data that were presented in the original manuscript are not affected by this alternative interpretation." Tarmo P. The authors note that the following grant should be added to the Acknowledgments: "NIH Grant AG002132." The authors note "The method used for exogenous expression of Ca V 1.2 channels in ref. 32 was incorrectly described as 'viral transduction' in the text. In fact, Yang et al. created transgenic mice with inducible, cardiomyocyte-specific expression of exogenous Ca V 1.2 channels regulated by a tetracycline-inducible promoter. When crossed with a transgenic mouse line expressing doxycycline-regulated reverse transcriptional activator under control of the α-myosin heavy chain protomer, the resulting double transgenic offspring expressed exogenous Ca V 1.2 channels in their cardiac myocytes after treatment with doxycycline. The authors regret the error in describing these methods."www.pnas.org/cgi

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Section: Comparison Between Bli and Other Techniques Used For Assessingmentioning

confidence: 94%

Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease

Watts

Giles

Grillo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

105

109

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“…Interestingly, APP/PSEN1 mice start to develop signs of cognitive impairment (demonstrate learning deficit in MWM hidden platform spatial navigation task) at 8 -12 months, approximately the same time that their PrP C -interacting A␤o reaches the average level observed in human AD brains. Moreover, regression analysis of these data demonstrates a very strong connection between PLISA and MWM navigation performance, highlighting the precision of PrP C -interacting A␤o levels in predicting cognitive impairment in APP/PSEN1 mice ( C -interacting A␤o measurement for cognitive impairment, we performed PLISA measurements throughout the life span of four widely used AD mouse models (in addition to APP/PSEN1 mice) (63,64) as follows: CRND8 transgenic mice (65), 3ϫ transgenic mice (53), 5ϫ FAD transgenic mice (67), and Tg2576 transgenic mice (68). Because of the differences in genetic backgrounds and slight variations under "Experimental Procedures" (for instance, the diameter of the maze used in the study), the direct interstrain comparison of cognitive performance between multiple AD mouse models using standard behavioral metrics (like the time the mouse spends in the target quadrant of the maze or the time the mouse takes to find the hidden platform) is extremely challenging.…”

Section: Levels Of Prp C -Interacting A␤o Increase With Age and Predimentioning

confidence: 99%

“…Tg2576 mice were performed in-house with the same colony as the A␤o measurements, whereas the behavioral data for CRND8 and 5ϫ FAD mice were extracted from the literature (65,69,70). All tested AD models demonstrated a progressive increase in PrP C -interacting A␤o; however, the rates of accumulation as well as maximal A␤o levels dramatically differed from strain to strain (Fig.…”

Section: Levels Of Prp C -Interacting A␤o Increase With Age and Predimentioning

confidence: 99%

“…All AD model mice but not WT animals demonstrated an increase in PrP c -interacting A␤ oligomers; however, the rates of accumulation varied greatly between models. To assess interstrain comparison of cognitive decline, behavioral data from in-house experiments (Tg2576, APP/PSEN1, 3ϫ Tg) as well as literature data (5ϫ FAD, CRND8 (65,69,70)) were converted into a normalized performance in Morris water maze hidden platform navigation task (normalized spatial learning deficit, nSLD) (d) and Morris water maze probe trials (nSMD) (e). SEC characterization of brain lysates from WT, 5ϫ FAD, Tg2576, and 3ϫ Tg mice coupled to PLISA (f) and A␤ 42 ELISA (g) have demonstrated results consistent with ones observed for APP/PSEN1 mice in Fig.…”

Section: Figure 3 Levels Of Prpmentioning

confidence: 99%

“…As described in Fig. 3, the normalized behavioral data are from in-house experiments (Tg2576, APP/PSEN1, 3ϫ Tg) as well as literature data (5ϫ FAD and CRND8 (65,69,70)). …”

Section: Prp C -Interacting Fraction and Size Of A␤o Pool Varies Betwmentioning

confidence: 99%

See 2 more Smart Citations

Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models

Kostylev¹,

Kaufman²,

Nygaard

et al. 2015

Journal of Biological Chemistry

116

132

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Background: Amyloid-␤ (A␤) oligomers are key in Alzheimer disease (AD) but are diverse and poorly characterized. Results: Multiple A␤ forms were measured across the life span of AD model mice and human AD brain. Conclusion: A␤ species interacting with prion protein were tightly linked to behavioral impairment. Significance: An A␤ oligomer subset with defined biochemical properties is present in multiple AD-relevant samples.

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Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid‐β oligomers

Gandy

Simon²,

Steele

et al. 2010

Annals of Neurology

125

136

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Objectives Recent evidence suggests that high molecular weight soluble oligomeric Aβ (oAβ) assemblies (also known as Aβ-derived diffusible ligands, or ADDLs) may represent a primary neurotoxic basis for cognitive failure in AD. To date, in vivo studies of oAβ/ADDLs have involved injection of assemblies purified from the cerebrospinal fluid (CSF) of human subjects with Alzheimer’s disease or from the conditioned media of Aβ-secreting cells into experimental animals. We sought to study the bioactivities of endogenously formed oAβ/ADDLs generated in situ from the physiological processing of human APP transgenes. Methods We produced and histologically characterized single transgenic mice overexpressing APPE693Q or APPE693Q X PS1ΔE9 bigenic mice. APPE693Q mice were studied in the Morris water maze (MWM) task at 6 and 12 months of age. Following the second MWM evaluation, mice were sacrificed, and brains were assayed for Aβtotal, Aβ40, Aβ42, and oAβ/ADDL by ELISA and were also histologically examined. Based on results from the oAβ/ADDL ELISA, we assigned individual APPE693Q mice to either an “undetectable oAβ/ADDLs group” or a “readily detectable oAβ/ADDLs group”. A days-to-criterion (DTC) analysis was used to determine delays in acquisition of the MWM task. Results Both single transgenic and bigenic mice developed intraneuronal accumulation of APP/Aβ, though only Dutch APPE693Q X PS1Δ9 bigenic mice developed amyloid plaques. The APPE693Q mice did not develop amyloid plaques at any age studied, up to 30 months. APPE693Q mice were tested for spatial learning and memory, and only 12-month old APPE693Q mice with readily detectable oAβ/ADDLs displayed a significant delay in acquisition of the MWM task when compared to NTg littermates. Interpretation These data suggest that cerebral oAβ/ADDL assemblies generated in brain in situ from human APP transgenes may be associated with cognitive impairment. We propose that a DTC analysis may be a sensitive method for assessing the cognitive impact in mice of endogenously generated oligomeric human Aβ assemblies.

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Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice

Cited by 68 publications

References 33 publications

Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease

Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease

Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models

Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid‐β oligomers

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