Synaptic vesicle endocytosis deficits underlie GBA-linked cognitive dysfunction in Parkinson’s disease and Dementia with Lewy bodies
2024
GBA Mutations and Cognitive Decline in Parkinson's Disease
publication
Author Information
Author(s): Chandra Sreeganga, Vidyadhara D J, Bäckström David, Chakraborty Risha, Ruan Jiapeng, Park Jae-Min, Mistry Pramod
Hypothesis
Mutant GBA contributes to cognitive decline in Parkinson's disease and Dementia with Lewy bodies through synaptic vesicle endocytosis deficits.
Conclusion
GBA mutations lead to cognitive deficits in Parkinson's disease through mechanisms that do not involve α-synuclein pathology.
Supporting Evidence
- Gba mutant mice showed early cognitive deficits without motor deficits.
- SNCA transgenic mice had motor deficits but no cognitive issues.
- Gba-SNCA double mutant mice exhibited both cognitive decline and motor deficits.
- Single-nucleus RNA sequencing revealed synaptic vesicle endocytosis defects in Gba mutant mice.
Takeaway
Some genes can make people forgetful in Parkinson's disease, even if they don't have the usual symptoms like shaking.
Methodology
The study used various mouse models to investigate cognitive and motor deficits and employed RNA sequencing and microscopy for analysis.
Digital Object Identifier (DOI)
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