Are you using 5xFAD mice to study Alzheimer’s disease? Our work out today @cp-neuron.bsky.social may be relevant to you 🐁🧠 Age and sex are known to influence Aβ plaque burden in these mice. Here, we found that the transgene parentage is another strong determinant. Thread below: (1/11) - ThreadSky

aosasmita.bsky.social • 37 days ago

Are you using 5xFAD mice to study Alzheimer’s disease? Our work out today @cp-neuron.bsky.social may be relevant to you 🐁🧠 Age and sex are known to influence Aβ plaque burden in these mice. Here, we found that the transgene parentage is another strong determinant.

Thread below: (1/11)

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aosasmita.bsky.social•37 days ago

First, we established that quantitative light-sheet microscopy (LSM) can reliably measure differences in plaque load. We demonstrated the age-related plaque increase in 5xFAD mice: plaque deposition occurs rapidly in the first 8 months, then numbers plateau over time. (2/11)

aosasmita.bsky.social•37 days ago

We confirmed the previously reported sex dimorphism in this model, with female 5xFAD mice showing double the plaque burden of age-matched males. This is especially evident in the cortex, showcasing the lag in plaque deposition in the cortex compared to the hippocampus. (3/11)

aosasmita.bsky.social•37 days ago

5xFAD mice are commonly used as heterozygotes to avoid the intensely high plaque loads seen in homozygous mice early on. This means breeding schemes often pair a WT with a 5xFAD mouse. But does it make a difference whether the mother or father carries the transgene? (4/11)

aosasmita.bsky.social•37 days ago

In fact, it does 🤯 Through LSM, we analyzed plaque burden in male 5xFAD mice with distinct parental sources for the transgene. Mice inheriting the transgene from the mother developed much lower plaque load (up to half in the cortex) than those with a paternal inheritance 🫢 (5/11)

aosasmita.bsky.social•37 days ago

We then asked if the effect lasts for multiple generations by tracing the grandparental lineage. Mice inheriting the transgene from 2 consecutive maternal sources had the lowest plaque load, but this additive effect by the grandparental source is minimal compared to the parental effect. (6/11)

aosasmita.bsky.social•37 days ago

Examined across both sexes, different ages, and importantly, separate mouse colonies, our work highlights the universal nature of this effect in congenic 5xFAD lines 🌎 Of note, this effect is not seen in heterozygous APPNLGF mice, suggesting it may be limited to transgenic mice. (7/11)

nicholasjsilva.bsky.social•36 days ago

Cool, congrats! 🥳

tepavcevicvanja.bsky.social•37 days ago

Wow! Congrats!!

aosasmita.bsky.social•37 days ago

Thanks Vanja!! Hope it was an enjoyable read.

tepavcevicvanja.bsky.social•37 days ago

It was totally surprising to me,learned lots of new stuff

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