Comparing familial Alzheimer’s disease and Sanfilippo syndrome childhood dementia at single-cell resolution

The Sanfilippo Children’s Foundation is proud to co-fund a project led by Dr Karissa Barthelson (Flinders University) with the Brain Foundation and Carthew Family Trust. Dr Barthelson will investigate the molecular similarities between Sanfilippo and early-onset familial Alzheimer’s disease with colleagues Associate Professor Michael Lardelli and Dr Luciano Martelotto from The University of Adelaide.

Genetic childhood dementias and adult-onset dementias may at first seem to be very different conditions. However, they can share many similar features, such as brain inflammation, accumulation of certain substances in the brain and other cell changes. This means that lessons learned in one form of dementia may also benefit people affected by other types.

In this project, which was awarded through the Brain Foundation’s 2023 competitive grants round and with additional co-funding support from Sanfilippo Children’s Foundation, Dr Barthelson and her colleagues hope to investigate similarities and differences between two forms of dementia: early-onset familial Alzheimer’s disease (EOfAD) and Sanfilippo. They will study which genes are turned on and off in different types of brain cells in zebrafish models of EOfAD and Sanfilippo type B.

This work expands on previous research by the team, funded by the Sanfilippo Children’s Foundation and Carthew Family Charity Trust, in which A/Prof Lardelli’s laboratory developed and tested new zebrafish models of Sanfilippo types A, B, and C.

The team had previously started looking into potential common disease mechanisms in EOfAD and Sanfilippo. They looked at gene activity levels using the whole brains of the young Sanfilippo fish and EOfAD fish models. Their initial analysis revealed intriguing clues about particular cell types and important metabolic pathways that were affected in the same way in both conditions. In this project, they will now look in more detail at the genes switched on and off in different types of brain cells, not just whole brains. 

“Comparing the two models may provide a better understanding of the similarities between these two forms of dementia and the specific types of cells and molecular pathways affected,” said Dr Lisa Melton, Head of Research at the Sanfilippo Children’s Foundation. “This may shed light on potential therapies for these and other neurodegenerative diseases.”

Read more about the project on the Brain Foundation’s website here.

Dr Karissa Barthelson completed her PhD in 2021 and, soon after, secured the prestigious ‘Race Against Dementia – Dementia Australia Research Foundation Post-doctoral Fellowship’. Her PhD focused on early-onset familial Alzheimer’s disease, though she now includes Sanfilippo syndrome in her work. By comparing the similarities and differences between these two forms of dementia, Dr Barthelson hopes to identify shared mechanisms and potential therapy avenues.

Project Summary

  • Project title: Single nuclei RNA-seq to compare the effects of mutations implicated in familial Alzheimer’s disease and Sanfilippo syndrome childhood dementia
  • Chief investigator: Dr Karissa Barthelson
  • Amount: $19,300 from Sanfilippo Children’s Foundation, $40,000 from Brain Foundation and $30,000 from Carthew Family Trust
  • Duration: 1 year
  • Location: Flinders University
  • Status: Active
  • Start date: January 2024

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