Ha, I do that as a warm-up! Jk, very impressive

Ah, so you use it to get enough info to decide if you are the right person to review it? And I agree, it is awesome just knowing it's out there and that people are reading it as soon as it's ready

Just curious, why is that? I just submitted a preprint for the first time and I'm not sure why I hesitated up to this point

Congratulations, Mark!!

Thanks, Mark! Couldn't have done it without you

Thanks, Jibran!!

8/8 Together, these data suggest that histone variants are vital to understanding chromatin dysregulation in AD and that opposing changes in male and female mice indicate a need for distinct therapeutic intervention.

7/n To test the functional relevance of H2A.Z, we found that H2A.Z.1 depletion in the mouse hippocampus IMPROVED memory, amyloid beta and tau pathology in females and WORSENED these markers in male mice, suggesting that H2A.Z has opposing effects on H2A.Z in male and female disease.

6/n Moreover, H2A.Z.1 depletion altered expression of distinct genes in each sex, suggesting that it is altering distinct disease pathways.

5/n Despite limited changes in H2A.Z occupancy in male mice, H2A.Z was more transcriptionally repressive in 5xFAD than in WT males, suggesting a shift in transcriptional regulation. H2A.Z was also more repressive in females than males.

4/n Female mice first showed a dramatic increase in H2A.Z at early disease stage, followed by decrease in later disease stages. In contrast, males had no change in early disease, but increased H2A.Z binding as disease progressed.

3/n To understand the function of H2A.Z dysregulation in the human brain, we used the 5xFAD mouse model of AD.  Sex differences were recapitulated in mice and varied with age.

2/n Here, we show that the histone variant H2A.Z is a sex-specific regulator of Alzheimer's disease.  First,  we show that H2A.Z levels decline of hippocampal chromatin of female AD patients,  while they increase in male AD patients.

1/n Histone variants are a key component of neuronal chromatin, but their role in AD is unknown. Histone variants are structurally and functionally district proteins that replace canonical histones in chromatin. Their occupancy in neurons increases with age, indicating a role in age-related disease.

What a great meeting, it was so good to see you and take a deep dive into your work

Very cool, congrats!!

Congratulations!!

Thank you!