2014年8月14日 · Behaviorally, PS19 mice display signs of age-associated cognitive impairment, including selective deficits in spatial learning and memory ability in the Morris water maze (Takeuchi et al., 2011). Other age-associated behavioral abnormalities include clasping and limb retraction when lifted by the tail, followed by limb weakness.

2020年7月14日 · Compared with PS19 mice carrying the common variant of TREM2, mice carrying the R47H variant exhibited less tau pathology, brain atrophy, glial activation, and synapse loss. Mice were characterized at 3 months, an age before the appearance of tau pathology in the parental PS19 line, and 9 months, a time when the parental line exhibits ...

2024年4月11日 · In PS19 mice, proteins (circles) whose levels were normalized by mAb2A7 support a variety of synaptic and signaling pathways. [Courtesy of Zhang et al., Neuron, 2024.] All told, Zhao and colleagues concluded that p-Tau217 is not only a marker of pathology but is itself pathogenic, by increasing tangles and altering proteostasis.

2024年5月21日 · ApoE3-PS19 mice (left) had twice as much aggregated tau (red) in the hippocampus as did ApoE3- R136S-PS19 mice (right). [Courtesy of Naguib et al., bioRxiv, 2024.] To probe cell responses, the researchers surveyed the transcriptomes of single nuclei from the hippocampi of 9- to 10-month-old PS19 males.

First author Sarah DeVos tested Tau ASO-12 in PS19 transgenic mice, which express P301S human tau at about five times the level of normal wild-type mouse tau. At five to six months of age, PS19 mice begin to develop tau deposits. By nine months of age they show extensive neurofibrillary tangles and neuronal cell death.

2024年4月30日 · Within the hippocampi of 9-month-old PS19 mice, about three months after neurofibrillary tangles had formed, lipid droplets accumulated, mainly in microglia (image below) and especially in those surrounding synapses containing phospho-tau inclusions. Droplet load tightly correlated with hippocampal neuron loss.

Levels of p-tau202 and p-tau396 were reduced in AAV-sTREM2 PS19 mice, compared with PS19 mice who received control vector, as was the activity of GSK3β, a kinase known to phosphorylate tau. Synapse loss. AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.

2018年2月7日 · PS19 mice were crossed with Trem2-/-mice or Trem2 +/+ mice, then the progeny of these crosses were further crossed to create Trem2-/-PS19 and Trem2 +/+ PS19 mice. During the course of these crosses, animals were moved onto a C57BL/6 genetic background. Phenotype Characterization

2017年10月26日 · By nine months, PS19 mice aggressively accumulate tau deposits, have extensive gliosis, and lose vast numbers of neurons. To their surprise, Leyns and colleagues found that at nine months, the PS19/TREM2 knockouts had substantially less atrophy in their brains than PS19 mice had, as judged by little ventricular enlargement, more cortical volume ...

2012年1月1日 · For example, PS19 mice were crossed to APPNL-G-F knock-in mice to create the APPNL-G-F/PS19 MAPTP301S line which develops features of Alzheimer’s disease pathology (Jiang et al., 2024). Transgenic rats expressing the mutant human gene, Tg12099 , have also been generated ( Ayers et al., 2024 ).