LBD: Understand Lewy body spreading and interactions with other AD/ADRD-related pathologies (Milestone 2.M)
In Progress
Timeline Start - End
2016 - 2027Research Implementation Area
Research on Disease MechanismsAD-Related Dementias Focus
LBD Pathogenesis and Mechanisms of Toxicity: Identify mechanisms of selective vulnerability, disease heterogeneity, disease spread/propagation, and interaction with other age-related pathologies as therapeutic targets.
Success Criteria
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At least one new project investigating α-synuclein spreading and α-synuclein interactions with other dementia-associated pathologies and how these interactions increase (or decrease) risk of symptomatic disease.
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At least two studies to understand why some brain cells are vulnerable to pathological alpha-synuclein accumulation while others are resistant.
Summary of Key Accomplishments
NINDS currently supports a Center Without Walls with four separate projects that are devoted to understanding devoted to understanding how the protein alpha-synuclein, which is often associated with LBD and Parkinson's disease, interacts with other AD/ADRD-related abnormal proteins, like beta-amyloid and tau, to initiate or accelerate brain disease in LBD. A request for applications (RFA NS21-006) was issued to invite research that seeks to understand how alpha-synuclein spreads and causes damage in the nervous system, and a number of applications were received and funded. Two recent research studies have shown that injecting alpha-synuclein into the brains of mice that carry gene mutations associated with Alzheimer's disease accelerates the rate at which beta-amyloid clumps deposit in the brain. These studies also show that abnormal deposits of tau and alpha-synuclein increase and brain inflammation increases.
The key accomplishments summary is current as of July 2022.
Accomplishments/Implementation Activities
Funding Initiatives
- RFA-NS-18-024: Lewy Body Dementia Center Without Walls (CWOW) (U54)
- RFA-NS-19-013: Lewy Body Dementia Center Without Walls (CWOW) (U54)
- RFA-NS-19-027: Human Three-Dimensional Cell Model Systems for Alzheimer's Disease-Related Dementias (ADRDs) (UG3/UH3)
- PAR-19-167: Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33)
- RFA-NS-21-006: Mechanisms of Pathological Spread of Abnormal Proteins in LBD and FTD (R01 Clinical Trial Not Allowed)
- RFA-NS-21-007: Mechanisms of Selective Vulnerability in LBD and FTD (R01 Clinical Trial Not Allowed)
Research Programs and Resources
- Lewy Body Dementia Center Without Walls (CWOW) (U54)
- Human Three-Dimensional Cell Model Systems for Alzheimer's Disease-Related Dementias (ADRDs) (UG3/UH3)
- Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33)
- Select projects funded in FY21
- Select projects funded in FY22