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Milestone 2.T

AD Related Dementias – Specific

Understanding the molecular, cellular and pathophysiology of α-synuclein in the context of non-motor brain areas.

Success Criteria

  • Develop in vitro and in vivo models that fit the known molecular pathology of LBD.
  • Establish research focused on α-synuclein biology in disease and non-disease states.
  • Support research on α-synuclein biology, pathology and cognitive impairment and dementia.

Summary of Key Accomplishments

NINDS supported the creation and banking of multiple induced pluripotent stem cell (iPSC) lines from individuals with LBD that are now freely available to researchers through the NINDS Human Cell and Data Repository. A recently funded grant is refining a mouse model of LBD in which alpha-synuclein spreads from the gut to the brain as the animal ages, which is thought to occur in humans with LBD.

Similarly, in another mouse model that carries an alpha synuclein gene mutation, clumps of abnormal alpha synuclein were found in the brainstem at 4 months, and then at a greater distance away in the motor cortex at 8 months, following injection of alpha-synuclein in a leg muscle, again supporting the idea that alpha synuclein spreads via cell to cell connections over time.

Research in brain tissue from humans shows that particular cognitive abilities (executive and visuospatial) were impaired to a greater degree if abnormal alpha synuclein (Lewy bodies) was found in the cortex compared to brain tissue that had AD-related changes in the same brain regions.

This information is current as of July 2022.

Research Implementation Area
AD Related Dementias - Specific
In Progress

Accomplishments/Implementation Activities

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