Iva Zovkic
@ivazovkic.bsky.social
Associate Professor and Canada Research Chair at University of Toronto Mississauga. Neuroepigenetics, Alzheimer's disease, memory
Pinned
Iva Zovkic
@ivazovkic.bsky.social
· Jun 2
Opposing effects of H2A.Z on memory, transcription and pathology in male and female Alzheimer's disease mice and patients
Alzheimer's disease (AD) is a devastating neurodegenerative disease that disproportionately impacts women, but underlying mechanisms for sex-divergent outcomes are unknown. Here, we show that the hist...
www.biorxiv.org
New preprint! In 2014, we showed that histone variants are new regulators of memory and ever since, we wondered if histone H2A.Z contributes to Alzheimer's. Using human brains and 5xFAD mice, we found that it depends on if you're male or female. Summary below. www.biorxiv.org/cgi/content/...
Ha, I do that as a warm-up! Jk, very impressive
June 27, 2025 at 11:38 AM
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
June 24, 2025 at 1:00 AM
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
June 23, 2025 at 11:32 PM
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
Reposted by Iva Zovkic
🚨🚨Job Alert🚨🚨!! Neuroscience, Physiology and Pharmacology are recruiting a new lecturer/associate professor! an amazing opportunity to join our fantastic dept! @ucl.ac.uk @ucllifesciences.bsky.social @uclnpp.bsky.social post here:
www.nature.com/naturecareer...
www.nature.com/naturecareer...
Lecturer / Associate Professor - London, England job with University College London (UCL) | 12840324
About usThe Division of Biosciences at UCL is one of the world's foremost centres for research and teaching in the biological sciences. We have an out
www.nature.com
June 19, 2025 at 12:59 PM
🚨🚨Job Alert🚨🚨!! Neuroscience, Physiology and Pharmacology are recruiting a new lecturer/associate professor! an amazing opportunity to join our fantastic dept! @ucl.ac.uk @ucllifesciences.bsky.social @uclnpp.bsky.social post here:
www.nature.com/naturecareer...
www.nature.com/naturecareer...
Congratulations, Mark!!
June 14, 2025 at 11:09 AM
Congratulations, Mark!!
Thanks, Mark! Couldn't have done it without you
June 2, 2025 at 12:19 PM
Thanks, Mark! Couldn't have done it without you
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.
June 2, 2025 at 12:02 PM
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.
June 2, 2025 at 12:02 PM
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.
June 2, 2025 at 12:02 PM
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.
June 2, 2025 at 12:02 PM
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.
June 2, 2025 at 12:01 PM
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.
June 2, 2025 at 12:01 PM
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.
June 2, 2025 at 12:00 PM
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.
June 2, 2025 at 12:00 PM
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.
New preprint! In 2014, we showed that histone variants are new regulators of memory and ever since, we wondered if histone H2A.Z contributes to Alzheimer's. Using human brains and 5xFAD mice, we found that it depends on if you're male or female. Summary below. www.biorxiv.org/cgi/content/...
Opposing effects of H2A.Z on memory, transcription and pathology in male and female Alzheimer's disease mice and patients
Alzheimer's disease (AD) is a devastating neurodegenerative disease that disproportionately impacts women, but underlying mechanisms for sex-divergent outcomes are unknown. Here, we show that the hist...
www.biorxiv.org
June 2, 2025 at 11:58 AM
New preprint! In 2014, we showed that histone variants are new regulators of memory and ever since, we wondered if histone H2A.Z contributes to Alzheimer's. Using human brains and 5xFAD mice, we found that it depends on if you're male or female. Summary below. www.biorxiv.org/cgi/content/...
What a great meeting, it was so good to see you and take a deep dive into your work
May 23, 2025 at 1:01 PM
What a great meeting, it was so good to see you and take a deep dive into your work
Wow wow wow! Congratulations on the @canacn.bsky.social new Investigator award to @markcembrowski.bsky.social. Absolutely fantastic seminar to celebrate a most deserved award. Congratulations!
May 22, 2025 at 10:01 PM
Wow wow wow! Congratulations on the @canacn.bsky.social new Investigator award to @markcembrowski.bsky.social. Absolutely fantastic seminar to celebrate a most deserved award. Congratulations!
Reposted by Iva Zovkic
If you are at @canacn.bsky.social , don't miss our symposium on Thurs 1:30 pm:
A genomics approach towards understanding sex differences in cognition, mental health, and neurodevelopment.
w @descalzi.bsky.social @ivazovkic.bsky.social @derubeislab.bsky.social @walkerde.bsky.social
See you there!
A genomics approach towards understanding sex differences in cognition, mental health, and neurodevelopment.
w @descalzi.bsky.social @ivazovkic.bsky.social @derubeislab.bsky.social @walkerde.bsky.social
See you there!
May 21, 2025 at 4:27 PM
If you are at @canacn.bsky.social , don't miss our symposium on Thurs 1:30 pm:
A genomics approach towards understanding sex differences in cognition, mental health, and neurodevelopment.
w @descalzi.bsky.social @ivazovkic.bsky.social @derubeislab.bsky.social @walkerde.bsky.social
See you there!
A genomics approach towards understanding sex differences in cognition, mental health, and neurodevelopment.
w @descalzi.bsky.social @ivazovkic.bsky.social @derubeislab.bsky.social @walkerde.bsky.social
See you there!
What an honor to host the @CAN_ACN public lecture by these 2 brilliant speakers. Thank you @sjo09.bsky.social and @barense.bsky.social for delivering such engaging lectures on memory to a packed house.
May 21, 2025 at 1:06 PM
What an honor to host the @CAN_ACN public lecture by these 2 brilliant speakers. Thank you @sjo09.bsky.social and @barense.bsky.social for delivering such engaging lectures on memory to a packed house.
Office views @uoftmississauga.bsky.social
May 16, 2025 at 6:10 PM
Office views @uoftmississauga.bsky.social
If you are in Toronto on Tuesday next week, please consider coming to see a FREE public lecture on memory, delivered by the amazing @sjo09.bsky.social and @barense.bsky.social . Tix at this link can-acn.org/meeting-2025... Please repost and hope to see you there!
CAN 2025 Public Lectures: Neuroscience of memory and tools for making our memories stronger – Canadian Association for Neuroscience
can-acn.org
May 14, 2025 at 7:15 PM
If you are in Toronto on Tuesday next week, please consider coming to see a FREE public lecture on memory, delivered by the amazing @sjo09.bsky.social and @barense.bsky.social . Tix at this link can-acn.org/meeting-2025... Please repost and hope to see you there!
Very cool, congrats!!
March 27, 2025 at 11:04 PM
Very cool, congrats!!