Dataset Information

Cryo-EM of Aβ fibrils from mouse models find tg-APP_ArcSwe fibrils resemble those found in patients with sporadic Alzheimer's disease.

ABSTRACT: The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer's disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APP_Swe and APP23 models. The tg-APP_ArcSwe mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer's disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer's disease.

SUBMITTER: Zielinski M

PROVIDER: S-EPMC10689242 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Cryo-EM of Aβ fibrils from mouse models find tg-APP<sub>ArcSwe</sub> fibrils resemble those found in patients with sporadic Alzheimer's disease.

Zielinski Mara M Peralta Reyes Fernanda S FS Gremer Lothar L Schemmert Sarah S Frieg Benedikt B Schäfer Luisa U LU Willuweit Antje A Donner Lili L Elvers Margitta M Nilsson Lars N G LNG Syvänen Stina S Sehlin Dag D Ingelsson Martin M Willbold Dieter D Schröder Gunnar F GF

Nature neuroscience 20231116 12

The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer's disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 an ...[more]

PMID: 37973869

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Project description:BACKGROUND: The source inoculum of gastrointestinal tract (GIT) microbes is largely influenced by delivery mode in full-term infants, but these influences may be decoupled in very low birth weight (VLBW, <1,500 g) neonates via conventional broad-spectrum antibiotic treatment. We hypothesize the built environment (BE), specifically room surfaces frequently touched by humans, is a predominant source of colonizing microbes in the gut of premature VLBW infants. Here, we present the first matched fecal-BE time series analysis of two preterm VLBW neonates housed in a neonatal intensive care unit (NICU) over the first month of life. RESULTS: Fresh fecal samples were collected every 3 days and metagenomes sequenced on an Illumina HiSeq2000 device. For each fecal sample, approximately 33 swabs were collected from each NICU room from 6 specified areas: sink, feeding and intubation tubing, hands of healthcare providers and parents, general surfaces, and nurse station electronics (keyboard, mouse, and cell phone). Swabs were processed using a recently developed 'expectation maximization iterative reconstruction of genes from the environment' (EMIRGE) amplicon pipeline in which full-length 16S rRNA amplicons were sheared and sequenced using an Illumina platform, and short reads reassembled into full-length genes. Over 24,000 full-length 16S rRNA sequences were produced, generating an average of approximately 12,000 operational taxonomic units (OTUs) (clustered at 97% nucleotide identity) per room-infant pair. Dominant gut taxa, including Staphylococcus epidermidis, Klebsiella pneumoniae, Bacteroides fragilis, and Escherichia coli, were widely distributed throughout the room environment with many gut colonizers detected in more than half of samples. Reconstructed genomes from infant gut colonizers revealed a suite of genes that confer resistance to antibiotics (for example, tetracycline, fluoroquinolone, and aminoglycoside) and sterilizing agents, which likely offer a competitive advantage in the NICU environment. CONCLUSIONS: We have developed a high-throughput culture-independent approach that integrates room surveys based on full-length 16S rRNA gene sequences with metagenomic analysis of fecal samples collected from infants in the room. The approach enabled identification of discrete ICU reservoirs of microbes that also colonized the infant gut and provided evidence for the presence of certain organisms in the room prior to their detection in the gut.

Dataset Information

Cryo-EM of Aβ fibrils from mouse models find tg-APP_ArcSwe fibrils resemble those found in patients with sporadic Alzheimer's disease.

Publications

Cryo-EM of Aβ fibrils from mouse models find tg-APP<sub>ArcSwe</sub> fibrils resemble those found in patients with sporadic Alzheimer's disease.

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Dataset Information

Cryo-EM of Aβ fibrils from mouse models find tg-APPArcSwe fibrils resemble those found in patients with sporadic Alzheimer's disease.

Publications

Cryo-EM of Aβ fibrils from mouse models find tg-APP<sub>ArcSwe</sub> fibrils resemble those found in patients with sporadic Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Cryo-EM of Aβ fibrils from mouse models find tg-APP_ArcSwe fibrils resemble those found in patients with sporadic Alzheimer's disease.