Early-onset Amyloid Deposition and Cognitive Deficits in Transgenic Mice Expressing a Double Mutant Form of Amyloid Precursor Protein 695

Chishti, M. Azhar; Yang, Dun-Shen; Janus, Christopher; Phinney, Amie L.; Horne, Patrick; Pearson, Jacqueline; Strome, Robert; Zuker, Noah B.; Loukides, James; French, Jacqueline A.; Turner, Sherry; Lozza, Gianluca; Grilli, Mariagrazia; Kunicki, Suzanne; Morissette, Céline; Paquette, Julie; Gervais, Francine; Bergeron, Catherine; Fraser, Paul E.; Carlson, George A.; George-Hyslop, Peter St; Westaway, David

doi:10.1074/jbc.m100710200

Cited by 855 publications

(963 citation statements)

References 70 publications

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“…While improvements in this parameter were noted in TgPS1delta E9/APPSwe mice deleted for the PrP gene, 52 there was no such effect of Prnp genotype in the J20 line of TgAD mice. 53 TgCRND8 mice 58 are a yet different line of TgAPP mice with more profound deposition of Aβ, starting at 3 months of age, and in our own trial studies 90% of neonatal mice lacking one copy of Prnp did not survive to 100 days of age (Fig. 2), in contrast to an earlier figures of 40-60% mortality.…”

Section: Proteolytic Pathwayscontrasting

confidence: 48%

“…2), in contrast to an earlier figures of 40-60% mortality. 58 Two interpretations here are that (1) a modifier gene governing postnatal mortality has been introduced in the genetic background of the Prnp 0/0 mice, or that (2) the presence of a wt Prnp gene (and presumably PrP C ) protects against APP overexpression. Inevitably, the task of weighing PrP C 's contribution in AD models is entangled in the limitations of said models, which most typically lack neuronal loss, and lack florid tauopathy deriving from endogenous tau.…”

Section: Proteolytic Pathwaysmentioning

confidence: 99%

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The P’s and Q’s of cellular PrP-Aβ interactions

Westaway

Jhamandas

2012

Prion

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Section: Proteolytic Pathwayscontrasting

confidence: 48%

Section: Proteolytic Pathwaysmentioning

confidence: 99%

The P’s and Q’s of cellular PrP-Aβ interactions

Westaway

Jhamandas

2012

Prion

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“…Frequently used models include PDAPP (Games et al , 1995), Tg2576 (Hsiao et al , 1996), APP23 (Sturchler‐Pierrat et al , 1997), J20 (Mucke et al , 2000), and TgCRND8 (Chishti et al , 2001). The APP constructs differ among the lines: They include APP695, APP770, and minigenes.…”

Section: First‐generation Mouse Modelsmentioning

confidence: 99%

“…Crossbreeding with particular mouse strains increase premature death in some lines (Tg2576 and TgCRND8; Carlson et al , 1997; Chishti et al , 2001). …”

Section: Limitations Of First‐generation Mouse Modelsmentioning

confidence: 99%

APP mouse models for Alzheimer's disease preclinical studies

et al. 2017

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Animal models of human diseases that accurately recapitulate clinical pathology are indispensable for understanding molecular mechanisms and advancing preclinical studies. The Alzheimer's disease (AD) research community has historically used first‐generation transgenic (Tg) mouse models that overexpress proteins linked to familial AD (FAD), mutant amyloid precursor protein (APP), or APP and presenilin (PS). These mice exhibit AD pathology, but the overexpression paradigm may cause additional phenotypes unrelated to AD. Second‐generation mouse models contain humanized sequences and clinical mutations in the endogenous mouse App gene. These mice show Aβ accumulation without phenotypes related to overexpression but are not yet a clinical recapitulation of human AD. In this review, we evaluate different APP mouse models of AD, and review recent studies using the second‐generation mice. We advise AD researchers to consider the comparative strengths and limitations of each model against the scientific and therapeutic goal of a prospective preclinical study.

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“…Transgenic hemizygous CRND8 male and female mice, harboring a double-mutant gene of APP695 (Chishti et al, 2001) with a (C57)/ (C57/C3H) genetic background, and non-Tg hybrid (C57)/(C57/C3H) wild type (wt) control littermate mice were used following the ECC (DL 116/92, Directive 86/609/EEC) and National guidelines for animal care. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Italian Ministry of Health (Permit Number: 283/2012-B).…”

Section: Ethics Statementmentioning

confidence: 99%

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

Luccarini

Grossi

Rigacci

et al. 2015

Neurobiology of Aging

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a b s t r a c tAmyloid-ß (Aß) fragments, oligomeric Aß aggregates, and pyroglutamylated-Aß peptides, as well as epigenetic mechanisms and autophagy dysfunction all appear to contribute in various ways to Alzheimer's disease progression. We previously showed that dietary supplementation of oleuropein aglycone, a natural phenol abundant in the extra virgin olive oil, can be protective by reducing Aß42 deposits in the brain of young and middle-aged TgCRND8 mice. Here, we extended our study to aged TgCRND8 mice showing increased pE3-Aß in the brain deposits. We report that oleuropein aglycone is active against glutaminylcyclase-catalyzed pE3-Aß generation reducing enzyme expression and interferes both with Aß42 and pE3-Aß aggregation. Moreover, the phenol astonishingly activates neuronal autophagy even in mice at advanced stage of pathology, where it increases histone 3 and 4 acetylation, which matches both a decrease of histone deacetylase 2 expression and a significant improvement of synaptic function. The occurrence of these functional, epigenetic, and histopathologic beneficial effects even at a late stage of the pathology suggests that the phenol could be beneficial at the therapeutic, in addition to the prevention, level.

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Early-onset Amyloid Deposition and Cognitive Deficits in Transgenic Mice Expressing a Double Mutant Form of Amyloid Precursor Protein 695

Cited by 855 publications

References 70 publications

The P’s and Q’s of cellular PrP-Aβ interactions

The P’s and Q’s of cellular PrP-Aβ interactions

APP mouse models for Alzheimer's disease preclinical studies

Oleuropein aglycone protects against pyroglutamylated-3 amyloid-ß toxicity: biochemical, epigenetic and functional correlates

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