Is a type of fat responsible for damage in the brain in dementia with Lewy bodies?
Dr Daniel Erskine
1 January 2023 - 31 December 2026
Full project name:
Lipids, lysosomes and mitochondria: towards a unified understanding of Lewy body dementia
Dementia with Lewy bodies (DLB) is the third most common cause of dementia, for which there are currently no disease-modifying treatments.
Many of the treatments in development target a protein called alpha-synuclein and stop it sticking together. However, Dr Erskine thinks that these drugs might not be as effective as stopping changes to a type of fat called sphingolipids.
Dr Erskine’s and others now think that sphingolipids cause alpha-synuclein to stick together, damage the cell's batteries – mitochondria, and block the cell's waste disposal system.
Understanding how the disease causes damage to the brain is vital in finding new drug targets to help discover a life-changing treatment.
What will they do?
Dr Erskine will test the idea that changes to sphingolipids, a type of fat, contribute to dementia with Lewy bodies, by affecting the protein alpha-synuclein.
He will use post-mortem brain tissue to establish the extent of damage to sphingolipids during DLB. Firstly, Dr Erskine will investigate whether changes to the way fat is processed impacts the build-up of the protein alpha-synuclein and whether it causes mitochondria to not work properly.
Dr Erskine thinks the Lewy bodies capture these faulty cellular batteries, potentially in a protective manner, encapsulating, capturing and reducing the build-up of damaged mitochondria.
He will also use a technique he developed as part of his Alzheimer’s Research UK Fellowship to look at human brain tissue from neurosurgical patients to determine if the fatty sphingolipid increases the likelihood that alpha-synuclein spreads through the brain.
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