APP mouse models for Alzheimer's disease preclinical studies
Hiroki Sasaguri,Hiroki Sasaguri,Per Nilsson,Per Nilsson,Shoko Hashimoto,Kenichi Nagata,Takashi Saito,Takashi Saito,Bart De Strooper,Bart De Strooper,John Hardy,Robert Vassar,Bengt Winblad,Takaomi C. Saido +13 more
TLDR
Different APP mouse models of AD are evaluated, the comparative strengths and limitations of each model are considered against the scientific and therapeutic goal of a prospective preclinical study, and recent studies using the second‐generation mice are reviewed.Abstract:
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.read more
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Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression.
Wang Xinyi,Sun Guangqiang,Feng Teng,Jing Zhang,Xun Huang,Tao Wang,Zuoquan Xie,Xingkun Chu,Jun Yang,Huan Wang,Shuaishuai Chang,Yanxue Gong,Lingfei Ruan,Guanqun Zhang,Siyuan Yan,Wen Lian,Chen Du,Dabing Yang,Qingli Zhang,Feifei Lin,Jia Liu,Haiyan Zhang,Changrong Ge,Shifu Xiao,Jian Ding,Meiyu Geng +25 more
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The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
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Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. The role of amyloid in dementia and stroke
Blas Frangione,Jorge Ghiso +1 more
TL;DR: Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidsosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the ameloid protein.
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The Major Risk Factors for Alzheimer's Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques.
Carlo Sala Frigerio,Carlo Sala Frigerio,Leen Wolfs,Nicola Fattorelli,Nicola Thrupp,Iryna Voytyuk,Inga Schmidt,Renzo Mancuso,Wei Ting Chen,Maya E. Woodbury,Gyan Srivastava,Thomas Möller,Eloise Hudry,Sudeshna Das,Takaomi C. Saido,Eric Karran,Bradley T. Hyman,V. Hugh Perry,V. Hugh Perry,Mark Fiers,Bart De Strooper,Bart De Strooper +21 more
TL;DR: Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus of male and female AppNL-G-F mice over time demonstrate that progressive amyloid-b accumulation accelerates two main activated microglia states that are also present during normal aging.
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