The senile plaque: Morphological differences in APP knock‐in mice brains by fixatives by Rikuya Yoshimura, Tomohiro Miyasaka, Satoru Funamoto, Takashi Saito, Takaomi C. Saido, Masaya Ikegawa, Nobuto Kakuda

“…Abstract The morphology of senile plaques depends on the APP knock‐in mice brain fixative. Solid forms of senile plaques were detected in APP knock‐in mice after formic acid treatment with Davidson's and Bouin's fluid fixative as the brain of AD patients. …”
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Behavioral and neuropathological characterization over the adult lifespan of the human tau knock-in mouse by Matthew J. Benskey, Spencer Panoushek, Takashi Saito, Takashi Saito, Takaomi C. Saido, Tessa Grabinski, Nicholas M. Kanaan, Nicholas M. Kanaan

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Hippocampal functional connectivity across age in an App knock-in mouse model of Alzheimer's disease by Zachery D. Morrissey, Zachery D. Morrissey, Zachery D. Morrissey, Jin Gao, Jin Gao, Liang Zhan, Weiguo Li, Weiguo Li, Weiguo Li, Igor Fortel, Takaomi Saido, Takashi Saito, Arnold Bakker, Arnold Bakker, Scott Mackin, Olusola Ajilore, Orly Lazarov, Alex D. Leow, Alex D. Leow, Alex D. Leow

“…Importantly, disruption of the default mode network, including the hippocampus, has been implicated in AD.MethodsTo examine the role of functional network connectivity changes in the early stages of AD, we performed resting-state functional magnetic resonance imaging (rs-fMRI) using a mouse model harboring three familial AD mutations (AppNL-G-F/NL-G-F knock-in, APPKI) in female mice in early, middle, and late age groups. …”
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Amelioration of Alzheimer’s Disease by Gut-Pancreas-Liver-Brain Interaction in an App Knock-In Mouse Model by Mayumi Minamisawa, Yuma Sato, Eitarou Ishiguro, Tetsuyuki Taniai, Taiichi Sakamoto, Gota Kawai, Takashi Saito, Takaomi C. Saido

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Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease by Hendrik Nieraad, Natasja de Bruin, Olga Arne, Martine C. J. Hofmann, Mike Schmidt, Takashi Saito, Takaomi C. Saido, Robert Gurke, Dominik Schmidt, Uwe Till, Michael J. Parnham, Gerd Geisslinger

“…In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel <i>App^NL-G-F</i> knock-in mouse model for AD, simulating an early stage of the disease. …”
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Age-Dependent Behavioral and Metabolic Assessment of AppNL−G−F/NL−G−F Knock-in (KI) Mice by Shanshan Wang, Shanshan Wang, Taiga Ichinomiya, Taiga Ichinomiya, Taiga Ichinomiya, Paul Savchenko, Paul Savchenko, Swetha Devulapalli, Swetha Devulapalli, Dongsheng Wang, Dongsheng Wang, Gianna Beltz, Gianna Beltz, Takashi Saito, Takaomi C. Saido, Steve L. Wagner, Hemal H. Patel, Hemal H. Patel, Brian P. Head, Brian P. Head

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Proteomic alterations in the brain and blood–brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer’s disease by Shingo Ito, Ryotaro Yagi, Seiryo Ogata, Takeshi Masuda, Takashi Saito, Takaomi Saido, Sumio Ohtsuki

“…This study aimed to investigate the relationship between BBB alterations and AD progression in terms of amyloid-β peptide (Aβ) accumulation in the brains of humanized amyloid precursor protein knock-in (APP-KI) mice. Methods Brain Aβ accumulation was examined using immunohistochemical analysis. …”
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T-type calcium channel enhancer SAK3 promotes dopamine and serotonin releases in the hippocampus in naive and amyloid precursor protein knock-in mice. by Shuo Wang, Yasushi Yabuki, Kazuya Matsuo, Jing Xu, Hisanao Izumi, Kenji Sakimura, Takashi Saito, Takaomi C Saido, Kohji Fukunaga

“…SAK3 (0.5 mg/kg, p.o.) administration also significantly elevated DA and 5-HT releases in the hippocampal CA1 region of amyloid-precursor protein (APP)NL-GF knock-in (KI) mice. Moreover, hippocampal DA and 5-HT contents were significantly decreased in APPNL-GF KI mice. …”
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Impairment in novelty-promoted memory via behavioral tagging and capture before apparent memory loss in a knock-in model of Alzheimer’s disease by Tabitha Broadbelt, Menekse Mutlu-Smith, Daniel Carnicero-Senabre, Takaomi C. Saido, Takashi Saito, Szu-Han Wang

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Early memory deficits and extensive brain network disorganization in the AppNL-F/MAPT double knock-in mouse model of familial Alzheimer’s disease by Christopher Borcuk, Céline Héraud, Karine Herbeaux, Margot Diringer, Élodie Panzer, Jil Scuto, Shoko Hashimoto, Takaomi C. Saido, Takashi Saito, Romain Goutagny, Demian Battaglia, Chantal Mathis

“…The AppNL-F/MAPT double knock-in (dKI) model with humanized β-amyloid peptide (Aβ) and tau was used to investigate both memory and network dysfunctions at an early stage. …”
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Cerebral Aβ deposition precedes reduced cerebrospinal fluid and serum Aβ42/Aβ40 ratios in the App NL−F/NL−F knock-in mouse model of Alzheimer’s disease by Emelie Andersson, Nina Schultz, Takashi Saito, Takaomi C. Saido, Kaj Blennow, Gunnar K. Gouras, Henrik Zetterberg, Oskar Hansson

“…In the present study, we aim to investigate such relationships using App knock-in mouse models of preclinical AD. Methods CSF, serum, and brain tissue were collected from 3- to 18-month-old App NL−F/NL−F knock-in mice (n = 48) and 2–18-month-old App NL/NL knock-in mice (n = 35). …”
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Effects of high‐fat diet on nutrient metabolism and cognitive functions in young APPKINL‐G‐F/NL‐G‐F mice by Wei Wang, Daisuke Tanokashira, Yudai Shibayama, Ryuhei Tsuji, Megumi Maruyama, Chiemi Kuroiwa, Takashi Saito, Takaomi C. Saido, Akiko Taguchi

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Prenatal stress aggravates age-dependent cognitive decline, insulin signaling dysfunction, and the pro-inflammatory response in the APPNL-F/NL-F mouse model of Alzheimer's disease by Ewa Trojan, Katarzyna Curzytek, Paulina Cieślik, Joanna M. Wierońska, Johannes Graff, Władysław Lasoń, Takashi Saito, Takaomi C. Saido, Agnieszka Basta-Kaim

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Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models by Laura Sebastian Monasor, Stephan A Müller, Alessio Vittorio Colombo, Gaye Tanrioever, Jasmin König, Stefan Roth, Arthur Liesz, Anna Berghofer, Anke Piechotta, Matthias Prestel, Takashi Saito, Takaomi C Saido, Jochen Herms, Michael Willem, Christian Haass, Stefan F Lichtenthaler, Sabina Tahirovic

“…Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid β (Aβ) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial Aβ Response Proteins (MARPs) that reflect heterogeneity of microglial alterations during early, middle and advanced stages of Aβ deposition and occur earlier in the APPPS1 mice. …”
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Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin by Xiao Liu, Qian Zhou, Jia-He Zhang, Ke-Yong Wang, Takashi Saito, Takaomi C. Saido, Xiaoying Wang, Xiumei Gao, Kagaku Azuma

“…We evaluated the pathologic brain alterations in young adult App knock-in model <i>App^NL-G-F</i> mice at 3 and 6 months of age, which corresponds to early-stage AD. …”
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Regional contributions of D-serine to Alzheimer’s disease pathology in male AppNL–G–F/NL–G–F mice by Xiance Ni, Xiance Ni, Ran Inoue, Ran Inoue, Yi Wu, Yi Wu, Tomoyuki Yoshida, Tomoyuki Yoshida, Keisuke Yaku, Takashi Nakagawa, Takashi Nakagawa, Takashi Saito, Takashi Saito, Takaomi C. Saido, Keizo Takao, Keizo Takao, Keizo Takao, Hisashi Mori, Hisashi Mori, Hisashi Mori

“…In the mammalian brain, it is produced by serine racemase (SRR) from L-serine, suggesting that dysregulation of L-serine, D-serine, or SRR may contribute to AD pathogenesis.Objective and methodsWe examined the contributions of D-serine to AD pathology in the AppNL–G–F/NL–G–F gene knock-in (APPKI) mouse model of AD. We first examined brain SRR expression levels and neuropathology in APPKI mice and then assessed the effects of long-term D-serine supplementation in drinking water on neurodegeneration. …”
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Alterations to parvalbumin-expressing interneuron function and associated network oscillations in the hippocampal – medial prefrontal cortex circuit during natural sleep in AppNL-G... by Erica S. Brady, Jessica Griffiths, Lilya Andrianova, Monika H. Bielska, Takashi Saito, Takaomi C. Saido, Andrew D. Randall, Francesco Tamagnini, Jonathan Witton, Michael T. Craig

“…This has prompted the development and use of knock-in mouse lines that express these genes at an endogenous level, such as the AppNL-G-F/NL-G-F mouse model used in the present study. …”
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β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease by Lulu Jiang, Lulu Jiang, Rebecca Roberts, Melissa Wong, Lushuang Zhang, Chelsea Joy Webber, Chelsea Joy Webber, Jenna Libera, Zihan Wang, Alper Kilci, Matthew Jenkins, Alejandro Rondón Ortiz, Luke Dorrian, Jingjing Sun, Jingjing Sun, Guangxin Sun, Sherif Rashad, Sherif Rashad, Caroline Kornbrek, Sarah Anne Daley, Sarah Anne Daley, Peter C. Dedon, Peter C. Dedon, Brian Nguyen, Weiming Xia, Weiming Xia, Takashi Saito, Takaomi C. Saido, Benjamin Wolozin, Benjamin Wolozin, Benjamin Wolozin, Benjamin Wolozin

“…IntroductionThe study of the pathophysiology study of Alzheimer’s disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular -amyloid (A) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration.MethodsThe humanized APPNL-G-F knock-in mouse line was crossed to the PS19 MAPTP301S, over-expression mouse line to create the dual APPNL-G-F/PS19 MAPTP301S line. …”
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