Anna Arutyunyan
@immunobananna.bsky.social
Postdoc in Lehner lab @sangerinstitute | PhD @sangerinstitute @Cambridge_Uni | BSc @miptru 🇷🇺🇦🇲
Genomics | Synthetic Biology | Immunology | Reproduction
Genomics | Synthetic Biology | Immunology | Reproduction
+ some great press releases
www.sanger.ac.uk/news_item/sc...
www.sanger.ac.uk/news_item/sc...
Scientists map the first step in Alzheimer’s protein aggregation and discover clues for future therapies
New research has found how the harmful protein linked to Alzheimer’s disease starts to aggregate.
www.sanger.ac.uk
June 12, 2025 at 12:54 PM
+ some great press releases
www.sanger.ac.uk/news_item/sc...
www.sanger.ac.uk/news_item/sc...
It is a very neat and elegant study which was so fun to work on, and I am very proud to see it out in the world!
@sangerinstitute.bsky.social @ibecbarcelona.eu @crg.eu
@sangerinstitute.bsky.social @ibecbarcelona.eu @crg.eu
June 12, 2025 at 12:54 PM
It is a very neat and elegant study which was so fun to work on, and I am very proud to see it out in the world!
@sangerinstitute.bsky.social @ibecbarcelona.eu @crg.eu
@sangerinstitute.bsky.social @ibecbarcelona.eu @crg.eu
12/
Last but by no means least, this was a great team effort - I had the absolute pleasure and privilege of working with brilliant Mireia (X: @mseumaar) and Andre @ajfaure.bsky.social, under the supervision of Ben @benlehner.bsky.social and Benedetta @bennibolo.bsky.social.
Last but by no means least, this was a great team effort - I had the absolute pleasure and privilege of working with brilliant Mireia (X: @mseumaar) and Andre @ajfaure.bsky.social, under the supervision of Ben @benlehner.bsky.social and Benedetta @bennibolo.bsky.social.
June 12, 2025 at 12:54 PM
12/
Last but by no means least, this was a great team effort - I had the absolute pleasure and privilege of working with brilliant Mireia (X: @mseumaar) and Andre @ajfaure.bsky.social, under the supervision of Ben @benlehner.bsky.social and Benedetta @bennibolo.bsky.social.
Last but by no means least, this was a great team effort - I had the absolute pleasure and privilege of working with brilliant Mireia (X: @mseumaar) and Andre @ajfaure.bsky.social, under the supervision of Ben @benlehner.bsky.social and Benedetta @bennibolo.bsky.social.
11/
The early stages of disease often hold the best targets for intervention. With this new approach, we have turned the invisible visible - and given us a powerful new lens on how Alzheimer’s begins 🧠🔬
The early stages of disease often hold the best targets for intervention. With this new approach, we have turned the invisible visible - and given us a powerful new lens on how Alzheimer’s begins 🧠🔬
June 12, 2025 at 12:54 PM
11/
The early stages of disease often hold the best targets for intervention. With this new approach, we have turned the invisible visible - and given us a powerful new lens on how Alzheimer’s begins 🧠🔬
The early stages of disease often hold the best targets for intervention. With this new approach, we have turned the invisible visible - and given us a powerful new lens on how Alzheimer’s begins 🧠🔬
10/
Our approach doesn’t just apply to Alzheimer’s disease.
It opens the door to studying dozens of other aggregation-prone proteins linked to disease - many of which have been extremely difficult to study until now.
Our approach doesn’t just apply to Alzheimer’s disease.
It opens the door to studying dozens of other aggregation-prone proteins linked to disease - many of which have been extremely difficult to study until now.
June 12, 2025 at 12:54 PM
10/
Our approach doesn’t just apply to Alzheimer’s disease.
It opens the door to studying dozens of other aggregation-prone proteins linked to disease - many of which have been extremely difficult to study until now.
Our approach doesn’t just apply to Alzheimer’s disease.
It opens the door to studying dozens of other aggregation-prone proteins linked to disease - many of which have been extremely difficult to study until now.
9/
Why this matters:
✅ Aβ42 mutations cause familial Alzheimer’s disease
✅ Anti-Aβ42 antibodies are the only approved treatments that slow the disease
✅ Our work reveals how Aβ42 starts to go rogue - and gives clues about how to block it
Why this matters:
✅ Aβ42 mutations cause familial Alzheimer’s disease
✅ Anti-Aβ42 antibodies are the only approved treatments that slow the disease
✅ Our work reveals how Aβ42 starts to go rogue - and gives clues about how to block it
June 12, 2025 at 12:54 PM
9/
Why this matters:
✅ Aβ42 mutations cause familial Alzheimer’s disease
✅ Anti-Aβ42 antibodies are the only approved treatments that slow the disease
✅ Our work reveals how Aβ42 starts to go rogue - and gives clues about how to block it
Why this matters:
✅ Aβ42 mutations cause familial Alzheimer’s disease
✅ Anti-Aβ42 antibodies are the only approved treatments that slow the disease
✅ Our work reveals how Aβ42 starts to go rogue - and gives clues about how to block it
8/
In other words: the seeds of Alzheimer’s are planted in the very first molecular event of nucleation. We have now made a major step in understanding this reaction, which brings us closer to exploring novel therapeutic approaches to prevent it.
In other words: the seeds of Alzheimer’s are planted in the very first molecular event of nucleation. We have now made a major step in understanding this reaction, which brings us closer to exploring novel therapeutic approaches to prevent it.
June 12, 2025 at 12:54 PM
8/
In other words: the seeds of Alzheimer’s are planted in the very first molecular event of nucleation. We have now made a major step in understanding this reaction, which brings us closer to exploring novel therapeutic approaches to prevent it.
In other words: the seeds of Alzheimer’s are planted in the very first molecular event of nucleation. We have now made a major step in understanding this reaction, which brings us closer to exploring novel therapeutic approaches to prevent it.
7/
This is the first-ever large-scale map of how mutations shape the earliest events in protein aggregation.
This is the first-ever large-scale map of how mutations shape the earliest events in protein aggregation.
June 12, 2025 at 12:54 PM
7/
This is the first-ever large-scale map of how mutations shape the earliest events in protein aggregation.
This is the first-ever large-scale map of how mutations shape the earliest events in protein aggregation.
6/
We show that a few interactions (energetic couplings) between parts of Aβ42 are significant for the nucleation process. These interactions happen at the C-terminus of the protein and are a subset of those found in the final fibril structures from Alzheimer’s patients’ brains.
We show that a few interactions (energetic couplings) between parts of Aβ42 are significant for the nucleation process. These interactions happen at the C-terminus of the protein and are a subset of those found in the final fibril structures from Alzheimer’s patients’ brains.
June 12, 2025 at 12:54 PM
6/
We show that a few interactions (energetic couplings) between parts of Aβ42 are significant for the nucleation process. These interactions happen at the C-terminus of the protein and are a subset of those found in the final fibril structures from Alzheimer’s patients’ brains.
We show that a few interactions (energetic couplings) between parts of Aβ42 are significant for the nucleation process. These interactions happen at the C-terminus of the protein and are a subset of those found in the final fibril structures from Alzheimer’s patients’ brains.
5/
By tracking how each mutation affected the speed of fibril formation, we built a complete energetic map of the Aβ42 nucleation reaction. We show that mutations in the latter part of Aβ42 (C-terminus / hydrophobic core) are largely disruptive for nucleation.
By tracking how each mutation affected the speed of fibril formation, we built a complete energetic map of the Aβ42 nucleation reaction. We show that mutations in the latter part of Aβ42 (C-terminus / hydrophobic core) are largely disruptive for nucleation.
June 12, 2025 at 12:54 PM
5/
By tracking how each mutation affected the speed of fibril formation, we built a complete energetic map of the Aβ42 nucleation reaction. We show that mutations in the latter part of Aβ42 (C-terminus / hydrophobic core) are largely disruptive for nucleation.
By tracking how each mutation affected the speed of fibril formation, we built a complete energetic map of the Aβ42 nucleation reaction. We show that mutations in the latter part of Aβ42 (C-terminus / hydrophobic core) are largely disruptive for nucleation.
4/
So how do we study something we can’t see?
🔬yeast cells
📈kinetic nucleation assay
⚡️high-throughput mutagenesis → 🧬140,000+ combinatorial mutants of Aβ42 - protein that aggregates in Alzheimer’s disease
🧠machine learning and energetic modelling
So how do we study something we can’t see?
🔬yeast cells
📈kinetic nucleation assay
⚡️high-throughput mutagenesis → 🧬140,000+ combinatorial mutants of Aβ42 - protein that aggregates in Alzheimer’s disease
🧠machine learning and energetic modelling
June 12, 2025 at 12:54 PM
4/
So how do we study something we can’t see?
🔬yeast cells
📈kinetic nucleation assay
⚡️high-throughput mutagenesis → 🧬140,000+ combinatorial mutants of Aβ42 - protein that aggregates in Alzheimer’s disease
🧠machine learning and energetic modelling
So how do we study something we can’t see?
🔬yeast cells
📈kinetic nucleation assay
⚡️high-throughput mutagenesis → 🧬140,000+ combinatorial mutants of Aβ42 - protein that aggregates in Alzheimer’s disease
🧠machine learning and energetic modelling
3/
And yet, it may be the most important step in the disease process, which so far scientists have struggled to study and understand. If we could block nucleation, we might stop Alzheimer’s before it starts 🧠
And yet, it may be the most important step in the disease process, which so far scientists have struggled to study and understand. If we could block nucleation, we might stop Alzheimer’s before it starts 🧠
June 12, 2025 at 12:54 PM
3/
And yet, it may be the most important step in the disease process, which so far scientists have struggled to study and understand. If we could block nucleation, we might stop Alzheimer’s before it starts 🧠
And yet, it may be the most important step in the disease process, which so far scientists have struggled to study and understand. If we could block nucleation, we might stop Alzheimer’s before it starts 🧠
2/
This “nucleation” step is the molecular switch that kick-starts aggregation and makes it possible for fibrils to spread. To nucleate, amyloid peptides need to go through a high-energy transition state - that is notoriously difficult to capture.
This “nucleation” step is the molecular switch that kick-starts aggregation and makes it possible for fibrils to spread. To nucleate, amyloid peptides need to go through a high-energy transition state - that is notoriously difficult to capture.
June 12, 2025 at 12:54 PM
2/
This “nucleation” step is the molecular switch that kick-starts aggregation and makes it possible for fibrils to spread. To nucleate, amyloid peptides need to go through a high-energy transition state - that is notoriously difficult to capture.
This “nucleation” step is the molecular switch that kick-starts aggregation and makes it possible for fibrils to spread. To nucleate, amyloid peptides need to go through a high-energy transition state - that is notoriously difficult to capture.
1/
In >50 neurodegenerative diseases - including Alzheimer’s - “rogue” proteins aggregate into harmful structures called amyloid fibrils.
These fibrils are highly stable and toxic. But they don’t appear all at once, first, a few molecules must nucleate - spark 💥before the fire.
In >50 neurodegenerative diseases - including Alzheimer’s - “rogue” proteins aggregate into harmful structures called amyloid fibrils.
These fibrils are highly stable and toxic. But they don’t appear all at once, first, a few molecules must nucleate - spark 💥before the fire.
June 12, 2025 at 12:54 PM
1/
In >50 neurodegenerative diseases - including Alzheimer’s - “rogue” proteins aggregate into harmful structures called amyloid fibrils.
These fibrils are highly stable and toxic. But they don’t appear all at once, first, a few molecules must nucleate - spark 💥before the fire.
In >50 neurodegenerative diseases - including Alzheimer’s - “rogue” proteins aggregate into harmful structures called amyloid fibrils.
These fibrils are highly stable and toxic. But they don’t appear all at once, first, a few molecules must nucleate - spark 💥before the fire.